Starting

Initialising…

BCORL1

Final classification

VUS

BCORL1 c.643_798dup · p.His215_Pro266dup

BCORL1

The BCORL1 c.643_798dup (p.His215_Pro266dup) variant has not been observed in somatic cancer records in COSMIC and has not been reported in ClinVar.

Gene

BCORL1

Transcript

NM_021946.4

HGVS · transcript:coding

NM_021946.4:c.643_798dup

Consequence

N/A

GRCh38

chrX:130013408 T>TGTGCCCCACTCTGTTCCAGATGCATTCCAGGTTCCCCTCTCCGTCCCTGCCCCAGTCCCCCATTCAGGGCTTGTTCCAGTCCAAGTTGCCACTTCGGTTCCAGCTCCTTCCCCTCCCTTAGCACCTGTCCCGGCTCTGGCTCCAGCGCCACCGTCA

GRCh37

chrX:129147384 T>TGTGCCCCACTCTGTTCCAGATGCATTCCAGGTTCCCCTCTCCGTCCCTGCCCCAGTCCCCCATTCAGGGCTTGTTCCAGTCCAAGTTGCCACTTCGGTTCCAGCTCCTTCCCCTCCCTTAGCACCTGTCCCGGCTCTGGCTCCAGCGCCACCGTCA

Basis gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting; combination = 1 supporting, which maps to VUS. ▾

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting; combination = 1 supporting, which maps to VUS.

Classification rationale

PM2 VUS

BCORL1 c.643_798dup

The BCORL1 c.643_798dup (p.His215_Pro266dup) variant has not been observed in somatic cancer records in COSMIC and has not been reported in ClinVar.¹ This variant is absent from gnomAD v2.1 and absent from gnomAD v4.1, with an observed population frequency of 0, which is below the 0.1% rarity threshold used for PM2.² In silico splice prediction does not support an abnormal splicing effect, with a SpliceAI maximum delta score of 0.00.³

PM2 → VUS

1 clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗

3 spliceai ↗

Gene diagram · NM_021946.4 · variants mapped to exon structure

BCORL1 NM_021946.4

Fetching transcript structure from UCSC…

Applied criteria · 1 met · select any tile

Met

Not met

Not assessed

N/A

Strength very strong supporting

Pathogenic evidence

PVS

Benign evidence

—

Rationale

Select a criterion.

Sources

Evidence used

Gaps remaining

Rule

—

Research & evidence

Population frequency

gnomAD v4.1

gnomAD v2.1

v4.1

Absent from gnomAD v4.1.

v2.1

Absent from gnomAD v2.1.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v2.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant is absent from ClinVar.

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

SpliceAI ↗

Functional Unknown Oncogenic Effect

OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BCORL1, a transcriptional repressor, is recurrently mutated in hematopoietic malignancies, astrocytomas, and intracranial germ cell tumors.

OncoKB ↗

COSMIC

Cancer hotspots

Somatic evidence Not in COSMIC / hotspots

COSMIC

This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).

Hotspots

This variant does not lie in a statistically significant hotspot.

COSMIC ↗ Hotspots ↗

Sources & reference links

7Sources

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC

Cancer hotspots