rs1555792878

Variant names:

• chr19-50414939-C-G
• NM_002691.4:c.2513C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-50414939-C-G
• chr19-50414939-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002691.4(POLD1):​c.2513C>G​(p.Pro838Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: POLD1 NM_002691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.37

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLD1	NM_002691.4	c.2513C>G	p.Pro838Arg	missense_variant	Exon 20 of 27	ENST00000440232.7	NP_002682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7	c.2513C>G	p.Pro838Arg	missense_variant	Exon 20 of 27	1	NM_002691.4	ENSP00000406046.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456448 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724206

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	26
DANN	Benign	0.95
DEOGEN2	Benign	0.35	T;.;.;T
Eigen	Benign	0.046
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.98	.;.;D;D
M_CAP	Benign	0.073	D
MetaRNN	Pathogenic	0.77	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.;.;L
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-7.9	D;.;.;.
REVEL	Benign	0.26
Sift	Benign	0.64	T;.;.;.
Sift4G	Benign	0.68	T;T;T;T
Polyphen		0.087	B;.;.;B
Vest4		0.85
MutPred		0.52		Gain of MoRF binding (P = 5e-04);.;.;Gain of MoRF binding (P = 5e-04);
MVP		0.66
MPC		0.85
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.63
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-50918196;