17-28357364-GC-GCC

Variant names:

• chr17-28357364-G-GC
• rs11448856
• NM_015584.5:c.84dupG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_015584.5(POLDIP2):​c.84dupG​(p.Pro29AlafsTer41) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: POLDIP2 NM_015584.5 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08
• Publications: 11 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 17-28357364-G-GC is Benign according to our data. Variant chr17-28357364-G-GC is described in ClinVar as Benign. ClinVar VariationId is 1249093.Status of the report is criteria_provided_single_submitter, 1 stars.

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.84dupG	p.Pro29AlafsTer41	frameshift	Exon 1 of 11	NP_056399.1	Q9Y2S7
	POLDIP2	NM_001290145.2		c.84dupG	p.Pro29AlafsTer41	frameshift	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.84dupG	p.Pro29AlafsTer41	frameshift	Exon 1 of 11	ENSP00000475924.2	Q9Y2S7
	POLDIP2	ENST00000902298.1		c.84dupG	p.Pro29AlafsTer41	frameshift	Exon 1 of 11	ENSP00000572357.1
	POLDIP2	ENST00000902300.1		c.84dupG	p.Pro29AlafsTer41	frameshift	Exon 1 of 11	ENSP00000572359.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 1.00 AC: 162253 AN: 162262 AF XY: 1.00

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 1.00 Hom.: 5887

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		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

Other links and lift over

dbSNP: rs11448856; hg19: chr17-26684390; COSMIC: COSV50228122; COSMIC: COSV50228122;