12-55693152-T-C

Variant names:

• chr12-55693152-T-C
• rs113651939
• NM_002206.3:c.2701A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002206.3(ITGA7):​c.2701A>G​(p.Ile901Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 1,613,798 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00097 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00075 (9 hom.)
• Consequence: ITGA7 NM_002206.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.47
• Publications: 7 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=0.009287894).
• BP6: Variant 12-55693152-T-C is Benign according to our data. Variant chr12-55693152-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 211211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000967 (147/152002) while in subpopulation EAS AF = 0.00838 (43/5130). AF 95% confidence interval is 0.0064. There are 3 homozygotes in GnomAd4. There are 67 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002206.3. 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
	ITGA7	NM_002206.3	MANE Select	c.2701A>G	p.Ile901Val	missense	Exon 20 of 25	NP_002197.2
	ITGA7	NM_001410977.1		c.2833A>G	p.Ile945Val	missense	Exon 21 of 26	NP_001397906.1
	ITGA7	NM_001144996.2		c.2713A>G	p.Ile905Val	missense	Exon 20 of 25	NP_001138468.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA7	ENST00000257879.11	TSL:1 MANE Select	c.2701A>G	p.Ile901Val	missense	Exon 20 of 25	ENSP00000257879.7
	ITGA7	ENST00000553804.6	TSL:1	c.2713A>G	p.Ile905Val	missense	Exon 20 of 25	ENSP00000452120.1
	ITGA7	ENST00000555728.5	TSL:5	c.2833A>G	p.Ile945Val	missense	Exon 21 of 26	ENSP00000452387.1

Frequencies

GnomAD3 genomes AF: 0.000909 AC: 138 AN: 151884 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000629

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00361

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00856

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00295 AC: 741 AN: 251328 AF XY: 0.00242

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.0151

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00908

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.000752 AC: 1100 AN: 1461796 Hom.: 9 Cov.: 33 AF XY: 0.000682 AC XY: 496 AN XY: 727180

African (AFR) AF: 0.000747 AC: 25 AN: 33476

American (AMR) AF: 0.0130 AC: 583 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26134

East Asian (EAS) AF: 0.00728 AC: 289 AN: 39700

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000594 AC: 66 AN: 1111938

Other (OTH) AF: 0.00181 AC: 109 AN: 60386

GnomAD4 genome AF: 0.000967 AC: 147 AN: 152002 Hom.: 3 Cov.: 31 AF XY: 0.000902 AC XY: 67 AN XY: 74280

African (AFR) AF: 0.000748 AC: 31 AN: 41450

American (AMR) AF: 0.00367 AC: 56 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00838 AC: 43 AN: 5130

South Asian (SAS) AF: 0.000417 AC: 2 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67998

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.000551 Hom.: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00256 AC: 311

Asia WGS AF: 0.0160 AC: 56 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Oct 26, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 14, 2014

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:3

Sep 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ITGA7: BS1, BS2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Sep 18, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nov 12, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0093	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.021
Sift	Benign	0.22	T
Sift4G	Benign	0.40	T
Polyphen		0.024	B
Vest4		0.20
MVP		0.40
MPC		0.14
ClinPred		0.0047	T
GERP RS		2.6
Varity_R		0.025
gMVP		0.18
Mutation Taster		=100/0	polymorphism

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: rs113651939; hg19: chr12-56086936; COSMIC: COSV107241501; COSMIC: COSV107241501;