rs1555789025

Positions:

• chr19-50398877-C-A
• chr19-50398877-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002691.4(POLD1):​c.26C>A​(p.Pro9Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POLD1 NM_002691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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]

POLD1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06240338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLD1	NM_002691.4	c.26C>A	p.Pro9Gln	missense_variant	2/27	ENST00000440232.7	NP_002682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7	c.26C>A	p.Pro9Gln	missense_variant	2/27	1	NM_002691.4	ENSP00000406046.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455770 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723846

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.28	T;.;.;.;T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.78	.;.;T;T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.062	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;.;.;.;N;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.0	N;.;.;.;.;.
REVEL	Benign	0.045
Sift	Benign	0.18	T;.;.;.;.;.
Sift4G	Benign	0.35	T;T;D;T;T;D
Polyphen		0.0010	B;.;.;.;B;.
Vest4		0.32
MutPred		0.16		Gain of MoRF binding (P = 0.0121);Gain of MoRF binding (P = 0.0121);Gain of MoRF binding (P = 0.0121);Gain of MoRF binding (P = 0.0121);Gain of MoRF binding (P = 0.0121);Gain of MoRF binding (P = 0.0121);
MVP		0.33
MPC		0.17
ClinPred		0.035	T
GERP RS		0.99
Varity_R		0.035
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-50902134; COSMIC: COSV101486927; COSMIC: COSV101486927;