Genetic Variant POLDIP2:p.Ala34Ala (chr17-28357347-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015584.5(POLDIP2):c.102C>T(p.Ala34Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,573,656 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0068 ( 14 hom., cov: 33)

Exomes 𝑓: 0.00061 ( 16 hom. )

Consequence

POLDIP2
NM_015584.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.284

Publications

0 publications found

Variant links:

Genes affected

POLDIP2 (HGNC:23781): (DNA polymerase delta interacting protein 2) This gene encodes a protein that interacts with the DNA polymerase delta p50 subunit, as well as with proliferating cell nuclear antigen. The encoded protein maybe play a role in the ability of the replication fork to bypass DNA lesions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

POLDIP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 17-28357347-G-A is Benign according to our data. Variant chr17-28357347-G-A is described in ClinVar as Benign. ClinVar VariationId is 789657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.284 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00684 (1042/152326) while in subpopulation AFR AF = 0.0239 (994/41580). AF 95% confidence interval is 0.0227. There are 14 homozygotes in GnomAd4. There are 502 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015584.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLDIP2	NM_015584.5	MANE Select	c.102C>T	p.Ala34Ala	synonymous	Exon 1 of 11	NP_056399.1	Q9Y2S7
	POLDIP2	NM_001290145.2		c.102C>T	p.Ala34Ala	synonymous	Exon 1 of 11	NP_001277074.1	B4DEM9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POLDIP2	ENST00000540200.6	TSL:1 MANE Select	c.102C>T	p.Ala34Ala	synonymous	Exon 1 of 11	ENSP00000475924.2	Q9Y2S7
POLDIP2	ENST00000902298.1		c.102C>T	p.Ala34Ala	synonymous	Exon 1 of 11	ENSP00000572357.1
POLDIP2	ENST00000902300.1		c.102C>T	p.Ala34Ala	synonymous	Exon 1 of 11	ENSP00000572359.1

Frequencies

GnomAD3 genomes

AF:

0.00684

AC:

1041

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0240

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00163

AC:

219

AN:

134698

AF XY:

0.00126

show subpopulations

Gnomad AFR exome

AF:

0.0410

Gnomad AMR exome

AF:

0.000874

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000498

Gnomad OTH exome

AF:

0.000312

GnomAD4 exome

AF:

0.000607

AC:

863

AN:

1421330

Hom.:

Cov.:

AF XY:

0.000501

AC XY:

354

AN XY:

706734

show subpopulations

African (AFR)

AF:

0.0238

AC:

725

AN:

30502

American (AMR)

AF:

0.000745

AC:

AN:

42940

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25274

East Asian (EAS)

AF:

0.00

AC:

AN:

36918

South Asian (SAS)

AF:

0.0000599

AC:

AN:

83474

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36202

Middle Eastern (MID)

AF:

0.000442

AC:

AN:

4528

European-Non Finnish (NFE)

AF:

0.0000145

AC:

AN:

1102352

Other (OTH)

AF:

0.00140

AC:

AN:

59140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

146

194

243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00684

AC:

1042

AN:

152326

Hom.:

Cov.:

AF XY:

0.00674

AC XY:

502

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0239

AC:

994

AN:

41580

American (AMR)

AF:

0.00229

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68014

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

148

197

246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00468

Hom.:

Bravo

AF:

0.00785

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.3

(source)

DANN

Benign

0.83

PhyloP100

0.28

PromoterAI

0.0055

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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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