chr19-50398570-C-CA

Position:

• chr19-50398570-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002691.4(POLD1):​c.-1-259dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.84 (23560 hom., cov: 0)
• Consequence: POLD1 NM_002691.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.527

Genes affected

POLD1 (HGNC:9175): (DNA polymerase delta 1, catalytic subunit) This gene encodes the 125-kDa catalytic subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-50398570-C-CA is Benign according to our data. Variant chr19-50398570-C-CA is described in ClinVar as [Benign]. Clinvar id is 1221567.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLD1	NM_002691.4	c.-1-259dup		intron_variant		ENST00000440232.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLD1	ENST00000440232.7	c.-1-259dup		intron_variant		1	NM_002691.4	P1

Frequencies

GnomAD3 genomes AF: 0.839 AC: 54075 AN: 64452 Hom.: 23559 Cov.: 0

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.776

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.834

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.839 AC: 54084 AN: 64476 Hom.: 23560 Cov.: 0 AF XY: 0.832 AC XY: 22838 AN XY: 27436

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.846

Gnomad4 FIN AF: 0.922

Gnomad4 NFE AF: 0.897

Gnomad4 OTH AF: 0.834

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 25, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35689550; hg19: chr19-50901827;