17-28357347-G-A

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

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

Conservation

PhyloP100: 0.284
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POLDIP2NM_015584.5 linkc.102C>T p.Ala34Ala synonymous_variant Exon 1 of 11 ENST00000540200.6 NP_056399.1 Q9Y2S7
POLDIP2NM_001290145.2 linkc.102C>T p.Ala34Ala synonymous_variant Exon 1 of 11 NP_001277074.1 Q9Y2S7B4DEM9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POLDIP2ENST00000540200.6 linkc.102C>T p.Ala34Ala synonymous_variant Exon 1 of 11 1 NM_015584.5 ENSP00000475924.2 Q9Y2S7
POLDIP2ENST00000618887.2 linkc.102C>T p.Ala34Ala synonymous_variant Exon 1 of 11 2 ENSP00000477665.2 B4DEM9

Frequencies

GnomAD3 genomes
AF:
0.00684
AC:
1041
AN:
152208
Hom.:
14
Cov.:
33
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
GnomAD3 exomes
AF:
0.00163
AC:
219
AN:
134698
Hom.:
6
AF XY:
0.00126
AC XY:
98
AN XY:
77968
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 SAS exome
AF:
0.0000464
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.:
16
Cov.:
32
AF XY:
0.000501
AC XY:
354
AN XY:
706734
show subpopulations
Gnomad4 AFR exome
AF:
0.0238
Gnomad4 AMR exome
AF:
0.000745
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000599
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000145
Gnomad4 OTH exome
AF:
0.00140
GnomAD4 genome
AF:
0.00684
AC:
1042
AN:
152326
Hom.:
14
Cov.:
33
AF XY:
0.00674
AC XY:
502
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0239
Gnomad4 AMR
AF:
0.00229
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00425
Alfa
AF:
0.00468
Hom.:
2
Bravo
AF:
0.00785

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
9.3
DANN
Benign
0.83
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201357006; hg19: chr17-26684373; API