NM_007215.4:c.544C>A

Variant names:

• chr17-64496425-G-T
• rs886037843
• NM_007215.4:c.544C>A

Variant summary

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

The NM_007215.4(POLG2):​c.544C>A​(p.Arg182Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000014 in 1,429,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R182R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: POLG2 NM_007215.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.66
• Publications: 0 publications found

Genes affected

POLG2 (HGNC:9180): (DNA polymerase gamma 2, accessory subunit) This gene encodes the processivity subunit of the mitochondrial DNA polymerase gamma. The encoded protein forms a heterotrimer containing one catalytic subunit and two processivity subunits. This protein enhances DNA binding and promotes processive DNA synthesis. Mutations in this gene result in autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions.[provided by RefSeq, Sep 2009]

MILR1 (HGNC:27570): (mast cell immunoglobulin like receptor 1) Predicted to enable transmembrane signaling receptor activity. Predicted to be involved in several processes, including cell-cell adhesion via plasma-membrane adhesion molecules; mast cell degranulation; and negative regulation of mast cell activation. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007215.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLG2	NM_007215.4	MANE Select	c.544C>A	p.Arg182Arg	synonymous	Exon 1 of 8	NP_009146.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLG2	ENST00000539111.7	TSL:1 MANE Select	c.544C>A	p.Arg182Arg	synonymous	Exon 1 of 8	ENSP00000442563.2
	POLG2	ENST00000585141.5	TSL:1	n.595C>A		non_coding_transcript_exon	Exon 1 of 5
	POLG2	ENST00000585104.2	TSL:3	n.515C>A		non_coding_transcript_exon	Exon 1 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1429330 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 705612

African (AFR) AF: 0.00 AC: 0 AN: 32562

American (AMR) AF: 0.00 AC: 0 AN: 42700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25242

East Asian (EAS) AF: 0.00 AC: 0 AN: 38990

South Asian (SAS) AF: 0.00 AC: 0 AN: 84616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5650

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1087870

Other (OTH) AF: 0.00 AC: 0 AN: 58746

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.91
PhyloP100		4.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.30		Position offset: -18

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

Other links and lift over

dbSNP: rs886037843; hg19: chr17-62492543;