Genetic Variant POLD2:c.-157T>C (chr7-44122210-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000452185.5(POLD2):c.-157T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,436,950 control chromosomes in the GnomAD database, including 47,776 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4468 hom., cov: 33)

Exomes 𝑓: 0.26 ( 43308 hom. )

Consequence

POLD2
ENST00000452185.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.244

Publications

17 publications found

Variant links:

Genes affected

POLD2 (HGNC:9176): (DNA polymerase delta 2, accessory subunit) This gene encodes the 50-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. The encoded protein is required for the stimulation of DNA polymerase delta activity by the processivity cofactor proliferating cell nuclear antigen (PCNA). Expression of this gene may be a marker for ovarian carcinomas. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 5. [provided by RefSeq, Mar 2012]

POLD2 Gene-Disease associations (from GenCC):

non-severe combined immunodeficiency due to polymerase delta deficiency
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

POLD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLD2	NM_006230.4 link	c.-56-101T>C		intron_variant	Intron 1 of 10	ENST00000610533.6	NP_006221.3	P49005A0A087WWF6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLD2	ENST00000610533.6 link	c.-56-101T>C		intron_variant	Intron 1 of 10	1	NM_006230.4	ENSP00000480186.2		P49005A0A087WWF6

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36132

AN:

152034

Hom.:

4463

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.361

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.272

GnomAD4 exome

AF:

0.256

AC:

328812

AN:

1284798

Hom.:

43308

Cov.:

AF XY:

0.252

AC XY:

156974

AN XY:

621802

show subpopulations

African (AFR)

AF:

0.185

AC:

5230

AN:

28214

American (AMR)

AF:

0.297

AC:

5824

AN:

19588

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

5191

AN:

18894

East Asian (EAS)

AF:

0.203

AC:

6977

AN:

34432

South Asian (SAS)

AF:

0.104

AC:

6450

AN:

62044

European-Finnish (FIN)

AF:

0.208

AC:

7689

AN:

36932

Middle Eastern (MID)

AF:

0.219

AC:

785

AN:

3592

European-Non Finnish (NFE)

AF:

0.270

AC:

277545

AN:

1027856

Other (OTH)

AF:

0.246

AC:

13121

AN:

53246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

12343

24686

37029

49372

61715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.238

AC:

36147

AN:

152152

Hom.:

4468

Cov.:

AF XY:

0.233

AC XY:

17302

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.198

AC:

8224

AN:

41520

American (AMR)

AF:

0.292

AC:

4460

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

916

AN:

3468

East Asian (EAS)

AF:

0.233

AC:

1207

AN:

5178

South Asian (SAS)

AF:

0.102

AC:

492

AN:

4826

European-Finnish (FIN)

AF:

0.199

AC:

2105

AN:

10586

Middle Eastern (MID)

AF:

0.250

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.261

AC:

17771

AN:

67984

Other (OTH)

AF:

0.272

AC:

573

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1440

2880

4320

5760

7200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.264

Hom.:

7087

Bravo

AF:

0.248

Asia WGS

AF:

0.163

AC:

569

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

8.9

(source)

DANN

Benign

0.61

PhyloP100

0.24

PromoterAI

-0.028

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

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

Publications

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7-44122210-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over