rs9905016

Variant names:

• chr17-64497225-T-C
• rs9905016
• XR_002957990.2:n.2082T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-64497225-T-C
• chr17-64497225-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The XR_002957990.2(MILR1):​n.2082T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,216 control chromosomes in the GnomAD database, including 11,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (11407 hom., cov: 33)
• Consequence: MILR1 XR_002957990.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.25
• Publications: 8 publications found

Genes affected

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]

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]

POLG2 Gene-Disease associations (from GenCC):

• progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• mitochondrial DNA depletion syndrome

  Inheritance: SD Classification: MODERATE Submitted by: Illumina
• autosomal dominant progressive external ophthalmoplegia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial DNA depletion syndrome 16 (hepatic type)

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-64497225-T-C is Benign according to our data. Variant chr17-64497225-T-C is described in ClinVar as Benign. ClinVar VariationId is 1239326.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLG2	NM_007215.4	c.-257A>G		upstream_gene_variant		ENST00000539111.7	NP_009146.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLG2	ENST00000539111.7	c.-257A>G		upstream_gene_variant		1	NM_007215.4	ENSP00000442563.2
POLG2	ENST00000585141.5	n.-206A>G		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42314 AN: 152098 Hom.: 11371 Cov.: 33

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0969

Gnomad OTH AF: 0.221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.279 AC: 42398 AN: 152216 Hom.: 11407 Cov.: 33 AF XY: 0.276 AC XY: 20528 AN XY: 74420

African (AFR) AF: 0.704 AC: 29208 AN: 41510

American (AMR) AF: 0.245 AC: 3746 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3472

East Asian (EAS) AF: 0.0338 AC: 175 AN: 5180

South Asian (SAS) AF: 0.109 AC: 529 AN: 4832

European-Finnish (FIN) AF: 0.115 AC: 1217 AN: 10606

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0969 AC: 6590 AN: 68006

Other (OTH) AF: 0.219 AC: 464 AN: 2116

Alfa AF: 0.161 Hom.: 6330

Bravo AF: 0.305

Asia WGS AF: 0.111 AC: 388 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.40
PhyloP100		-1.3
PromoterAI		0.079	Neutral

Splicing

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

Other links and lift over

dbSNP: rs9905016; hg19: chr17-62493343;