Starting

Initialising…

POLD1

Final classification

VUS

POLD1 c.203-13C>A · p.?

POLD1

The POLD1 c.203-13C>A (p.?) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.

Gene

POLD1

Transcript

NM_002691.4

HGVS · transcript:coding

NM_002691.4:c.203-13C>A

Consequence

N/A

GRCh38

chr19:50399358 C>A

GRCh37

chr19:50902615 C>A

Basis Generic ACMG/AMP 2015 final classification combination rules were used because no explicit official or custom gene-specific final-classification framework was available. ▾

Generic ACMG/AMP 2015 final classification combination rules were used because no explicit official or custom gene-specific final-classification framework was available.

Classification rationale

PM2 BP4 VUS

POLD1 c.203-13C>A

The POLD1 c.203-13C>A (p.?) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.¹ This variant is absent from gnomAD v2.1 and shows 0/1,602,912 alleles in gnomAD v4.1 (AF 0.0%), which is below the 0.1% rarity threshold and supports PM2 at supporting strength.² SpliceAI predicts no significant splice impact for this intronic change, with a maximum delta score of 0.15, which supports BP4 and does not support PP3.³

PM2 + BP4 → VUS

1 evidence.json:results.cosmicevidence.json:results.clinvar

2 evidence.json:results.gnomad.GNOMAD_V2_1evidence.json:results.gnomad.GNOMAD_V4_1

3 evidence.json:results.spliceai

Gene diagram · NM_002691.4 · variants mapped to exon structure

POLD1 NM_002691.4

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= 0; MAF= 0.00000%, 0/1602912 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/74744 alleles, homozygotes = 0).

v2.1

Absent from gnomAD v2.1.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

Absent · 0 / 1,602,912
0 hom

Not observed in any ancestry group.

+ 10 not observed (Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish))

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 = 0.15).

SpliceAI ↗

Functional No data

No calibrated functional assay or RNA evidence was identified for this variant.

OncoKB ↗

COSMIC

Somatic evidence

COSMIC

This variant has not previously been reported in somatic cancers (COSMIC).

Hotspots

This variant does not lie in a statistically significant cancer hotspot.

COSMIC ↗

Sources & reference links

6Sources

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC