17-28349133-C-T

Variant names:

• chr17-28349133-C-T
• rs34881086
• NM_015584.5:c.942G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_015584.5(POLDIP2):​c.942G>A​(p.Ala314Ala) 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 1,613,382 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (13 hom.)
• Consequence: POLDIP2 NM_015584.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.20

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]

LOC124903963 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-28349133-C-T is Benign according to our data. Variant chr17-28349133-C-T is described in ClinVar as [Benign]. Clinvar id is 789654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.2 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00649 (988/152306) while in subpopulation AFR AF= 0.0221 (918/41554). AF 95% confidence interval is 0.0209. There are 13 homozygotes in gnomad4. There are 481 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLDIP2	NM_015584.5	c.942G>A	p.Ala314Ala	synonymous_variant	Exon 10 of 11	ENST00000540200.6	NP_056399.1
POLDIP2	NM_001290145.2	c.888G>A	p.Ala296Ala	synonymous_variant	Exon 10 of 11		NP_001277074.1
LOC124903963	XR_007065687.1	n.201C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLDIP2	ENST00000540200.6	c.942G>A	p.Ala314Ala	synonymous_variant	Exon 10 of 11	1	NM_015584.5	ENSP00000475924.2
POLDIP2	ENST00000618887.2	c.888G>A	p.Ala296Ala	synonymous_variant	Exon 10 of 11	2		ENSP00000477665.2

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 987 AN: 152188 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00209 AC: 518 AN: 248132 Hom.: 5 AF XY: 0.00163 AC XY: 219 AN XY: 134664

Gnomad AFR exome AF: 0.0250

Gnomad AMR exome AF: 0.000553

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00597

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000267

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.000656 AC: 959 AN: 1461076 Hom.: 13 Cov.: 31 AF XY: 0.000553 AC XY: 402 AN XY: 726796

Gnomad4 AFR exome AF: 0.0219

Gnomad4 AMR exome AF: 0.000694

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00214

Gnomad4 SAS exome AF: 0.0000581

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.00138

GnomAD4 genome AF: 0.00649 AC: 988 AN: 152306 Hom.: 13 Cov.: 32 AF XY: 0.00646 AC XY: 481 AN XY: 74470

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00502

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00126 Hom.: 5

Bravo AF: 0.00731

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	1.1
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs34881086; hg19: chr17-26676159;