chr12-55693209-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_002206.3(ITGA7):c.2644G>A(p.Glu882Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 1,614,078 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0034 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0036 ( 28 hom. )

Consequence

ITGA7
NM_002206.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:9

Conservation

PhyloP100: 2.60

Publications

14 publications found

Variant links:

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

ITGA7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00966835).

BP6

Variant 12-55693209-C-T is Benign according to our data. Variant chr12-55693209-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 94041.We mark this variant Benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00343 (522/152226) while in subpopulation AMR AF = 0.00405 (62/15292). AF 95% confidence interval is 0.00361. There are 5 homozygotes in GnomAd4. There are 240 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA7	NM_002206.3 link	c.2644G>A	p.Glu882Lys	missense_variant	Exon 20 of 25	ENST00000257879.11	NP_002197.2	Q13683-7Q4LE35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA7	ENST00000257879.11 link	c.2644G>A	p.Glu882Lys	missense_variant	Exon 20 of 25	1	NM_002206.3	ENSP00000257879.7		Q13683-7

Frequencies

GnomAD3 genomes

AF:

0.00343

AC:

521

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00400

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00426

AC:

1072

AN:

251460

AF XY:

0.00458

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00266

Gnomad ASJ exome

AF:

0.0271

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00489

Gnomad OTH exome

AF:

0.00798

GnomAD4 exome

AF:

0.00359

AC:

5243

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

2691

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

33478

American (AMR)

AF:

0.00257

AC:

115

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0282

AC:

736

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00267

AC:

230

AN:

86254

European-Finnish (FIN)

AF:

0.000749

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0199

AC:

115

AN:

5766

European-Non Finnish (NFE)

AF:

0.00327

AC:

3634

AN:

1111982

Other (OTH)

AF:

0.00556

AC:

336

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

310

620

930

1240

1550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00343

AC:

522

AN:

152226

Hom.:

Cov.:

AF XY:

0.00323

AC XY:

240

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.000771

AC:

AN:

41530

American (AMR)

AF:

0.00405

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

107

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00228

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000472

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00400

AC:

272

AN:

68018

Other (OTH)

AF:

0.00994

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

103

129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00485

Hom.:

Bravo

AF:

0.00383

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00400

AC:

486

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00676

EpiControl

AF:

0.00599

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:9

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:2

Aug 21, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Variant reported in homozygous state in individual with congenital fiber-type disproportion - individual had hypotonia but pulmonary phenotypes were not reported. However, variant has high frequency, 5 homozygotes are present in ExAC, and Emory classifies as benign. -

Dec 05, 2017

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. -

Congenital muscular dystrophy due to integrin alpha-7 deficiency

Benign:3

Mar 19, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ITGA7: BP4, BS2 -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

ITGA7-related disorder

Benign:1

Nov 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;.;T;.;T

Eigen

Benign

0.012

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.90

D;D;D;D;D

MetaRNN

Benign

0.0097

T;T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.8

.;.;.;.;L

PhyloP100

2.6

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.099

T;T;T;T;T

Sift4G

Benign

0.54

T;T;T;T;T

Polyphen

0.31

B;.;.;B;B

Vest4

0.68

MVP

0.45

MPC

0.55

ClinPred

0.023

GERP RS

4.8

Varity_R

0.12

gMVP

0.39

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over