About SOX17
No gene-level summary was recorded for this case.
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.No gene-level summary was recorded for this case.
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
No pathogenic criterion marked as applied in the recorded assessment.
This variant is present at an allele frequency of 1.11% in gnomAD v4.1 (17,140/1,543,370 alleles, 139 homozygotes), exceeding the BA1 threshold of >1%. The highest subpopulation frequency is 1.32% in European (non-Finnish) (15,213/1,148,906 alleles, 122 homozygotes). The variant is too common to be a cause of a rare Mendelian disorder.
This variant is present at an allele frequency of 0.722% in gnomAD v2.1 (1,232/170,616 alleles, 10 homozygotes), exceeding the BS1 threshold of >0.3%. The highest subpopulation frequency is 1.21% in European (non-Finnish) (824/68,336 alleles, 7 homozygotes). The variant is more common than expected for a pathogenic variant causing a rare disorder.
NM_022454.3:c.972_977dup encodes an in-frame duplication of Gln324 and His325 (p.Gln324_His325dup), which reside within a repetitive low-complexity poly-QH tract in the C-terminal region of SOX17. The native sequence contains multiple QH dipeptide repeats (QMQPQHQHQHQHQHQHH...), and the duplication inserts an additional QH unit into this repetitive region. In-frame duplications within repetitive regions without known function are consistent with benign variation under BP3.
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BA1 stand-alone benign, BS1 strong benign, BP3 supporting benign; combination = 1 stand-alone benign + 1 strong benign + 1 supporting benign, which maps to Benign.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 17,140 / 1,543,370 alleles. Recorded AF 0.0111056. Recorded homozygote count 139.
This variant is present in gnomAD v2.1 (AF= 0.00722089; MAF= 0.72209%, 1232/170616 alleles, homozygotes = 10) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0120581; MAF= 1.20581%, 824/68336 alleles, homozygotes = 7); grpmax FAF= 0.0118218.
This variant is present in gnomAD-Canada v1.0 (AF= 0.010005437737901033, 184/18390 alleles, homozygotes = 1).
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
2 Benign · 1 Likely benign. ClinVar API review status: criteria provided, conflicting classifications.
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. SOX17 encodes a transcription factor involved in embryonic development and cell fate. Methylation and downregulation of SOX17 are found in colon, live
This variant has previously been reported in somatic cancers (COSMIC; COSV52026813, n = 3 times).
This variant does not lie in a statistically significant hotspot.
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
29 criteria with recorded statuses: 3 met · 21 not met · 0 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
BA1 is met: this variant has an allele frequency of 1.11% in gnomAD v4.1 (17,140/1,543,370 alleles, 139 homozygotes), exceeding the stand-alone benign threshold of >1%.
BS1 is met: the variant is present at 0.722% in gnomAD v2.1 (1,232/170,616 alleles, 10 homozygotes), exceeding the strong benign threshold of >0.3%.
BP3 is met: the variant is an in-frame duplication (p.Gln324_His325dup) within a repetitive low-complexity poly-QH tract in the SOX17 C-terminal region, consistent with a benign in-frame insertion in a repetitive region without known function.
Under generic ACMG/AMP 2015 combination rules, BA1 alone is sufficient for a Benign classification. Independently, BS1 (strong benign) plus BP3 (supporting benign) also exceeds the Likely Benign threshold of one strong benign plus one supporting benign criterion.
The variant is classified in ClinVar as Benign (2 clinical laboratories) and Likely benign (1 clinical laboratory) under Variation ID 915867, consistent with the population evidence.
No criteria match.
No further detail was recorded.
No further detail was recorded.
No further detail was recorded.
No further detail was recorded.
Every interpreted variant in SOX17, mapped onto the exon structure of NM_022454.3. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| European (non-Finnish)15213 / 1,148,906 | 0.013122 hom |
| Remaining individuals605 / 60,150 | 0.016 hom |
| European (Finnish)393 / 48,480 | 0.00812 hom |
| South Asian544 / 84,718 | 0.00647 hom |
| Middle Eastern27 / 5,996 | 0.00452 hom |
| Amish3 / 912 | 0.0033 |
| Admixed American149 / 51,432 | 0.0029 |
| African/African American142 / 73,180 | 0.0019 |
| Ashkenazi Jewish43 / 28,636 | 0.0015 |
| East Asian21 / 40,960 | 0.00051 |
| European (non-Finnish)824 / 68,336 | 0.0127 hom |
| Remaining individuals61 / 5,274 | 0.0122 hom |
| European (Finnish)93 / 11,566 | 0.008 |
| South Asian131 / 23,210 | 0.00561 hom |
| Admixed American72 / 25,858 | 0.0028 |
| Ashkenazi Jewish18 / 8,450 | 0.0021 |
| African/African American25 / 15,520 | 0.0016 |
| East Asian8 / 12,402 | 0.00065 |
This variant is present in gnomAD v4.1 (AF= 0.0111056; MAF= 1.11056%, 17140/1543370 alleles, homozygotes = 139) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0132413; MAF= 1.32413%, 15213/1148906 alleles, homozygotes = 122); grpmax FAF= 0.0130646.
This variant is present in gnomAD v2.1 (AF= 0.00722089; MAF= 0.72209%, 1232/170616 alleles, homozygotes = 10) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0120581; MAF= 1.20581%, 824/68336 alleles, homozygotes = 7); grpmax FAF= 0.0118218.
This variant is present in gnomAD-Canada v1.0 (AF= 0.010005437737901033, 184/18390 alleles, homozygotes = 1).
No further detail was recorded.
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
2 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
This variant is present in gnomAD v4.1 (AF= 0.0111056; MAF= 1.11056%, 17140/1543370 alleles, homozygotes = 139) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0132413; MAF= 1.32413%, 15213/1148906 alleles, homozygotes = 122); grpmax FAF= 0.0130646.
This variant is present in gnomAD v2.1 (AF= 0.00722089; MAF= 0.72209%, 1232/170616 alleles, homozygotes = 10) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0120581; MAF= 1.20581%, 824/68336 alleles, homozygotes = 7); grpmax FAF= 0.0118218.
This variant is present in gnomAD-Canada v1.0 (AF= 0.010005437737901033, 184/18390 alleles, homozygotes = 1).
This variant has been reported in ClinVar as Benign (2 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 915867)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. SOX17 encodes a transcription factor involved in embryonic development and cell fate. Methylation and downregulation of SOX17 are found in colon, live
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52026813, n = 3 times).
This variant does not lie in a statistically significant hotspot.