Genetic Variant POLD1:c.-1-260_-1-259dupAA (chr19-50398570-C-CAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_002691.4(POLD1):c.-1-260_-1-259dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.082 ( 768 hom., cov: 0)

Consequence

POLD1
NM_002691.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.527

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 19-50398570-C-CAA is Benign according to our data. Variant chr19-50398570-C-CAA is described in ClinVar as Benign. ClinVar VariationId is 1302817.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
POLD1	NM_002691.4	MANE Select	c.-1-260_-1-259dupAA	intron	N/A	NP_002682.2	P28340
POLD1	NM_001256849.1		c.-4-257_-4-256dupAA	intron	N/A	NP_001243778.1	P28340
POLD1	NM_001438212.1		c.-1-260_-1-259dupAA	intron	N/A	NP_001425141.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POLD1	ENST00000440232.7	TSL:1 MANE Select	c.-1-281_-1-280insAA	intron	N/A	ENSP00000406046.1	P28340
POLD1	ENST00000595904.6	TSL:1	c.-1-281_-1-280insAA	intron	N/A	ENSP00000472445.1	M0R2B7
POLD1	ENST00000599857.7	TSL:1	c.-4-278_-4-277insAA	intron	N/A	ENSP00000473052.1	P28340

Frequencies

GnomAD3 genomes

AF:

0.0823

AC:

5185

AN:

63032

Hom.:

768

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.0639

Gnomad ASJ

AF:

0.0883

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.0198

Gnomad MID

AF:

0.0714

Gnomad NFE

AF:

0.0581

Gnomad OTH

AF:

0.0861

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

GnomAD4 genome

AF:

0.0823

AC:

5188

AN:

63052

Hom.:

768

Cov.:

AF XY:

0.0833

AC XY:

2233

AN XY:

26800

show subpopulations

African (AFR)

AF:

0.145

AC:

2099

AN:

14432

American (AMR)

AF:

0.0639

AC:

259

AN:

4052

Ashkenazi Jewish (ASJ)

AF:

0.0883

AC:

185

AN:

2094

East Asian (EAS)

AF:

0.110

AC:

186

AN:

1690

South Asian (SAS)

AF:

0.106

AC:

111

AN:

1044

European-Finnish (FIN)

AF:

0.0198

AC:

AN:

506

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0581

AC:

2203

AN:

37922

Other (OTH)

AF:

0.0847

AC:

AN:

732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

159

319

478

638

797

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over