NM_002206.3:c.1952G>A

Variant names:

• chr12-55695573-C-T
• rs1800974
• NM_002206.3:c.1952G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002206.3(ITGA7):​c.1952G>A​(p.Arg651His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,612,848 control chromosomes in the GnomAD database, including 233,196 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R651C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.50 (20346 hom., cov: 28)
  • Exomes 𝑓: 0.53 (212850 hom.)
• Consequence: ITGA7 NM_002206.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0920
• Publications: 56 publications found

Genes affected

ITGA7 (HGNC:6143): (integrin subunit alpha 7) The protein encoded by this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. They mediate a wide spectrum of cell-cell and cell-matrix interactions, and thus play a role in cell migration, morphologic development, differentiation, and metastasis. This protein functions as a receptor for the basement membrane protein laminin-1. It is mainly expressed in skeletal and cardiac muscles and may be involved in differentiation and migration processes during myogenesis. Defects in this gene are associated with congenital myopathy. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Feb 2009]

ITGA7 Gene-Disease associations (from GenCC):

• congenital muscular dystrophy due to integrin alpha-7 deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• congenital fiber-type disproportion myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.2049737E-7).
• BP6: Variant 12-55695573-C-T is Benign according to our data. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in CliVar as Benign. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA7	NM_002206.3	c.1952G>A	p.Arg651His	missense_variant	Exon 14 of 25	ENST00000257879.11	NP_002197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA7	ENST00000257879.11	c.1952G>A	p.Arg651His	missense_variant	Exon 14 of 25	1	NM_002206.3	ENSP00000257879.7

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75757 AN: 151416 Hom.: 20333 Cov.: 28

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.481

GnomAD2 exomes AF: 0.592 AC: 148860 AN: 251382 AF XY: 0.593

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.714

Gnomad ASJ exome AF: 0.456

Gnomad EAS exome AF: 0.939

Gnomad FIN exome AF: 0.650

Gnomad NFE exome AF: 0.512

Gnomad OTH exome AF: 0.549

GnomAD4 exome AF: 0.530 AC: 773992 AN: 1461314 Hom.: 212850 Cov.: 46 AF XY: 0.534 AC XY: 388526 AN XY: 726986

African (AFR) AF: 0.318 AC: 10645 AN: 33462

American (AMR) AF: 0.700 AC: 31316 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 12032 AN: 26132

East Asian (EAS) AF: 0.935 AC: 37106 AN: 39698

South Asian (SAS) AF: 0.692 AC: 59697 AN: 86236

European-Finnish (FIN) AF: 0.641 AC: 34259 AN: 53414

Middle Eastern (MID) AF: 0.498 AC: 2870 AN: 5762

European-Non Finnish (NFE) AF: 0.498 AC: 554066 AN: 1111516

Other (OTH) AF: 0.530 AC: 32001 AN: 60374

GnomAD4 genome AF: 0.500 AC: 75800 AN: 151534 Hom.: 20346 Cov.: 28 AF XY: 0.514 AC XY: 38044 AN XY: 74034

African (AFR) AF: 0.332 AC: 13710 AN: 41240

American (AMR) AF: 0.600 AC: 9149 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1575 AN: 3466

East Asian (EAS) AF: 0.935 AC: 4785 AN: 5116

South Asian (SAS) AF: 0.714 AC: 3426 AN: 4796

European-Finnish (FIN) AF: 0.652 AC: 6865 AN: 10522

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34607 AN: 67856

Other (OTH) AF: 0.485 AC: 1018 AN: 2098

Alfa AF: 0.509 Hom.: 93299

Bravo AF: 0.485

TwinsUK AF: 0.497 AC: 1842

ALSPAC AF: 0.498 AC: 1921

ESP6500AA AF: 0.340 AC: 1497

ESP6500EA AF: 0.508 AC: 4373

ExAC AF: 0.585 AC: 71060

Asia WGS AF: 0.768 AC: 2667 AN: 3478

EpiCase AF: 0.497

EpiControl AF: 0.494

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Jan 04, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 18, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 20, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital muscular dystrophy due to integrin alpha-7 deficiency Benign:2

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.0019	.;.;T;.;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.0035	N
LIST_S2	Benign	0.79	T;T;T;T;T
MetaRNN	Benign	9.2e-7	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;.;.;.;N
PhyloP100		0.092
PrimateAI	Benign	0.21	T
PROVEAN	Benign	1.4	N;N;N;N;N
REVEL	Benign	0.088
Sift	Benign	0.28	T;T;T;T;T
Sift4G	Benign	0.45	T;T;T;T;T
Polyphen		0.0	B;.;.;B;B
Vest4		0.066
MPC		0.21
ClinPred		0.0057	T
GERP RS		-0.71
Varity_R		0.013
gMVP		0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs1800974; hg19: chr12-56089357; COSMIC: COSV57696745; COSMIC: COSV57696745;