Analysis in progress

Initialising…

complete

This report is still being assembled — sections appear as each stage finishes. It isn't final yet.

EZHIP

Final classification

VUS

EZHIP c.162C>T · p.Pro54=

EZHIP

Gene

EZHIP

Transcript

NM_203407.3

HGVS · transcript:coding

NM_203407.3:c.162C>T

Consequence

N/A

GRCh38

chrX:51407178 C>T

GRCh37

chrX:51150030 C>T

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, BP7 supporting benign; combination = 1 supporting + 1 supporting benign, 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, BP7 supporting benign; combination = 1 supporting + 1 supporting benign, which maps to VUS.

Classification rationale

PM2 BP7 VUS

EZHIP c.162C>T

NM_203407.3:c.162C>T (p.Pro54=) is a synonymous variant in EZHIP with no predicted splice impact (SpliceAI max delta = 0.00) and is present at extremely low frequency in gnomAD v4.1 (1/570,831 alleles).¹ BP7 (supporting benign) is met: the variant is synonymous and SpliceAI predicts no splicing impact.² PM2 (supporting) is met: the variant is present at 0.00018% in gnomAD v4.1, below the 0.1% threshold.³ One supporting benign criterion (BP7) and one supporting pathogenic criterion (PM2) are met; these do not combine to a definitive classification under generic ACMG/AMP 2015 rules. The variant is classified as a Variant of Uncertain Significance (VUS).⁴

PM2 + BP7 → VUS

1 spliceai ↗gnomad_v4 ↗

2 spliceai ↗

3 gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

4 generic_acmg_combination_rules

Gene diagram · NM_203407.3 · variants mapped to exon structure

EZHIP NM_203407.3

Fetching transcript structure from UCSC…

Applied criteria · 2 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

This variant is present in gnomAD v4.1 (AF= 1.75183e-06; MAF= 0.00018%, 1/570831 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.23171e-06; MAF= 0.00032%, 1/309434 alleles, homozygotes = 0).

v2.1

Absent from gnomAD v2.1.

🇨🇦 CA

Absent from gnomAD-Canada v1.0.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

0.00018% · 1 / 570,831
0 hom

European (non-Finnish)

1 / 309,434

0.00032%

+ 9 not observed (Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American)

gnomAD v2.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD Canada 🇨🇦

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v4 ↗ gnomAD v2 ↗ gnomAD 🇨🇦 ↗

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 identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

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

8Sources

ClinVar

gnomAD v2.1

gnomAD v4.1

gnomAD-Canada

SpliceAI

OncoKB

COSMIC

Cancer hotspots