NM_002206.3:c.2004-19G>A

Variant names:

• chr12-55694989-C-T
• rs2293410
• NM_002206.3:c.2004-19G>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.2004-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,609,194 control chromosomes in the GnomAD database, including 231,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19847 hom., cov: 30)
  • Exomes 𝑓: 0.53 (211529 hom.)
• Consequence: ITGA7 NM_002206.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0820
• Publications: 17 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 (BayesDel_noAF=-0.81).
• BP6: Variant 12-55694989-C-T is Benign according to our data. Variant chr12-55694989-C-T is described in ClinVar as Benign. ClinVar VariationId is 94037.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.

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.2004-19G>A		intron	N/A	NP_002197.2
	ITGA7	NM_001410977.1		c.2136-19G>A		intron	N/A	NP_001397906.1
	ITGA7	NM_001144996.2		c.2016-19G>A		intron	N/A	NP_001138468.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA7	ENST00000257879.11	TSL:1 MANE Select	c.2004-19G>A		intron	N/A	ENSP00000257879.7
	ITGA7	ENST00000553804.6	TSL:1	c.2016-19G>A		intron	N/A	ENSP00000452120.1
	ITGA7	ENST00000557058.2	TSL:5	n.1400G>A		non_coding_transcript_exon	Exon 8 of 18

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74210 AN: 151740 Hom.: 19835 Cov.: 30

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.474

GnomAD2 exomes AF: 0.592 AC: 142508 AN: 240686 AF XY: 0.593

Gnomad AFR exome AF: 0.289

Gnomad AMR exome AF: 0.713

Gnomad ASJ exome AF: 0.456

Gnomad EAS exome AF: 0.939

Gnomad FIN exome AF: 0.651

Gnomad NFE exome AF: 0.513

Gnomad OTH exome AF: 0.548

GnomAD4 exome AF: 0.528 AC: 769965 AN: 1457336 Hom.: 211529 Cov.: 36 AF XY: 0.533 AC XY: 386661 AN XY: 724982

African (AFR) AF: 0.277 AC: 9280 AN: 33460

American (AMR) AF: 0.700 AC: 31189 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 12028 AN: 26124

East Asian (EAS) AF: 0.934 AC: 37073 AN: 39672

South Asian (SAS) AF: 0.692 AC: 59650 AN: 86162

European-Finnish (FIN) AF: 0.641 AC: 32360 AN: 50508

Middle Eastern (MID) AF: 0.498 AC: 2871 AN: 5766

European-Non Finnish (NFE) AF: 0.498 AC: 553685 AN: 1110770

Other (OTH) AF: 0.528 AC: 31829 AN: 60298

GnomAD4 genome AF: 0.489 AC: 74251 AN: 151858 Hom.: 19847 Cov.: 30 AF XY: 0.503 AC XY: 37331 AN XY: 74220

African (AFR) AF: 0.294 AC: 12158 AN: 41416

American (AMR) AF: 0.596 AC: 9117 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1573 AN: 3464

East Asian (EAS) AF: 0.935 AC: 4800 AN: 5134

South Asian (SAS) AF: 0.715 AC: 3437 AN: 4810

European-Finnish (FIN) AF: 0.652 AC: 6887 AN: 10570

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34608 AN: 67866

Other (OTH) AF: 0.478 AC: 1007 AN: 2106

Alfa AF: 0.478 Hom.: 3792

Bravo AF: 0.473

Asia WGS AF: 0.767 AC: 2666 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jul 18, 2012

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

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.5
DANN	Benign	0.62
PhyloP100		0.082
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: rs2293410; hg19: chr12-56088773;