17-28357368-T-G

Variant names:

• chr17-28357368-T-G
• rs17856014
• NM_015584.5:c.81A>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_015584.5(POLDIP2):​c.81A>C​(p.Pro27Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: POLDIP2 NM_015584.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.494
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (Cadd=6.913).
• BP6: Variant 17-28357368-T-G is Benign according to our data. Variant chr17-28357368-T-G is described in ClinVar as Benign. ClinVar VariationId is 1236990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.494 with no splicing effect.

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.81A>C	p.Pro27Pro	synonymous	Exon 1 of 11	NP_056399.1	Q9Y2S7
	POLDIP2	NM_001290145.2		c.81A>C	p.Pro27Pro	synonymous	Exon 1 of 11	NP_001277074.1	B4DEM9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLDIP2	ENST00000540200.6	TSL:1 MANE Select	c.81A>C	p.Pro27Pro	synonymous	Exon 1 of 11	ENSP00000475924.2	Q9Y2S7
	POLDIP2	ENST00000902298.1		c.81A>C	p.Pro27Pro	synonymous	Exon 1 of 11	ENSP00000572357.1
	POLDIP2	ENST00000902300.1		c.81A>C	p.Pro27Pro	synonymous	Exon 1 of 11	ENSP00000572359.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.456 Hom.: 5886

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	6.9
PhyloP100		-0.49
PromoterAI		0.0075	Neutral

Splicing

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

Other links and lift over

dbSNP: rs17856014; COSMIC: COSV107983770; COSMIC: COSV107983770;