chr19-50416702-C-G

Variant names:

• chr19-50416702-C-G
• NM_002691.4:c.3046C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002691.4(POLD1):​c.3046C>G​(p.Arg1016Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,389,774 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: POLD1 NM_002691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.29

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]

ENSG00000142539 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLD1	NM_002691.4	c.3046C>G	p.Arg1016Gly	missense_variant	Exon 24 of 27	ENST00000440232.7	NP_002682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7	c.3046C>G	p.Arg1016Gly	missense_variant	Exon 24 of 27	1	NM_002691.4	ENSP00000406046.1
ENSG00000142539	ENST00000599632.1	c.253C>G	p.Arg85Gly	missense_variant	Exon 3 of 10	5		ENSP00000473233.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1389774 Hom.: 0 Cov.: 34 AF XY: 0.00000146 AC XY: 1 AN XY: 686308

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.26e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;.;.;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Pathogenic	0.98	.;.;D;D
M_CAP	Pathogenic	0.45	D
MetaRNN	Uncertain	0.71	D;D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.1	M;.;.;M
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.0	D;.;.;.
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D;.;.;.
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		0.89	P;.;.;P
Vest4		0.49
MutPred		0.54		Loss of MoRF binding (P = 0.0256);.;.;Loss of MoRF binding (P = 0.0256);
MVP		0.71
MPC		0.85
ClinPred		0.99	D
GERP RS		2.6
Varity_R		0.65
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50919959;