rs369613619

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7

The NM_002691.4(POLD1):c.3054G>A(p.Val1018Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,539,184 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V1018V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00097 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

POLD1
NM_002691.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:15

Conservation

PhyloP100: -0.680

Publications

3 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

mandibular hypoplasia-deafness-progeroid syndrome
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp
POLD1-related polyposis and colorectal cancer syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
colorectal cancer, susceptibility to, 10
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Polymerase proofreading-related adenomatous polyposis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
immunodeficiency 120
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
non-severe combined immunodeficiency due to polymerase delta deficiency
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

POLD1 links:

ENSG00000142539 (HGNC:):

ENSG00000142539 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.068).

BP6

Variant 19-50416710-G-A is Benign according to our data. Variant chr19-50416710-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 239329.

BP7

Synonymous conserved (PhyloP=-0.68 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002691.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POLD1	NM_002691.4	MANE Select	c.3054G>A	p.Val1018Val	synonymous	Exon 24 of 27	NP_002682.2	P28340
POLD1	NM_001308632.1		c.3132G>A	p.Val1044Val	synonymous	Exon 23 of 26	NP_001295561.1	M0R2B7
POLD1	NM_001256849.1		c.3054G>A	p.Val1018Val	synonymous	Exon 24 of 27	NP_001243778.1	P28340

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POLD1	ENST00000440232.7	TSL:1 MANE Select	c.3054G>A	p.Val1018Val	synonymous	Exon 24 of 27	ENSP00000406046.1	P28340
POLD1	ENST00000595904.6	TSL:1	c.3132G>A	p.Val1044Val	synonymous	Exon 24 of 27	ENSP00000472445.1	M0R2B7
POLD1	ENST00000599857.7	TSL:1	c.3054G>A	p.Val1018Val	synonymous	Exon 24 of 27	ENSP00000473052.1	P28340

Frequencies

GnomAD3 genomes

AF:

0.000973

AC:

148

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000502

AC:

AN:

137366

AF XY:

0.000414

show subpopulations

Gnomad AFR exome

AF:

0.000143

Gnomad AMR exome

AF:

0.000735

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000129

Gnomad NFE exome

AF:

0.000913

Gnomad OTH exome

AF:

0.000244

GnomAD4 exome

AF:

0.00114

AC:

1586

AN:

1386902

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

738

AN XY:

684676

show subpopulations

African (AFR)

AF:

0.000158

AC:

AN:

31558

American (AMR)

AF:

0.000726

AC:

AN:

35810

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25138

East Asian (EAS)

AF:

0.00

AC:

AN:

35796

South Asian (SAS)

AF:

0.00

AC:

AN:

79218

European-Finnish (FIN)

AF:

0.00110

AC:

AN:

38338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4216

European-Non Finnish (NFE)

AF:

0.00135

AC:

1455

AN:

1079028

Other (OTH)

AF:

0.00100

AC:

AN:

57800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

169

254

338

423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000972

AC:

148

AN:

152282

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41562

American (AMR)

AF:

0.00281

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00121

AC:

AN:

67992

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000803

Hom.:

Bravo

AF:

0.00125

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (7)

not specified (4)

Colorectal cancer, susceptibility to, 10 (2)

Hereditary cancer-predisposing syndrome (2)

Polymerase proofreading-related adenomatous polyposis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.2

(source)

DANN

Benign

0.85

PhyloP100

-0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over