NM_006230.4:c.1393dupC

Variant names:

• chr7-44114801-A-AG
• NM_006230.4:c.1393dupC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006230.4(POLD2):​c.1393dupC​(p.Leu465ProfsTer30) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: POLD2 NM_006230.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25

Genes affected

POLD2 (HGNC:9176): (DNA polymerase delta 2, accessory subunit) This gene encodes the 50-kDa catalytic subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. The encoded protein is required for the stimulation of DNA polymerase delta activity by the processivity cofactor proliferating cell nuclear antigen (PCNA). Expression of this gene may be a marker for ovarian carcinomas. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 5. [provided by RefSeq, Mar 2012]

AEBP1 (HGNC:303): (AE binding protein 1) This gene encodes a member of carboxypeptidase A protein family. The encoded protein may function as a transcriptional repressor and play a role in adipogenesis and smooth muscle cell differentiation. Studies in mice suggest that this gene functions in wound healing and abdominal wall development. Overexpression of this gene is associated with glioblastoma. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLD2	NM_006230.4	c.1393dupC	p.Leu465ProfsTer30	frameshift_variant	Exon 11 of 11	ENST00000610533.6	NP_006221.3
AEBP1	NM_001129.5	c.*540_*541insG		downstream_gene_variant		ENST00000223357.8	NP_001120.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLD2	ENST00000610533.6	c.1393dupC	p.Leu465ProfsTer30	frameshift_variant	Exon 11 of 11	1	NM_006230.4	ENSP00000480186.2
AEBP1	ENST00000223357.8	c.*540_*541insG		downstream_gene_variant		1	NM_001129.5	ENSP00000223357.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Dec 28, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with POLD2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the POLD2 gene (p.Leu500Profs*30). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 5 amino acid(s) of the POLD2 protein and extend the protein by 24 additional amino acid residues. -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-44154400;