rs2293413

Variant names:

• chr12-55703032-T-C
• rs2293413
• NM_002206.3:c.334+19A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-55703032-T-C
• chr12-55703032-T-G
• chr12-55703032-T-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.334+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,613,676 control chromosomes in the GnomAD database, including 235,371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20973 hom., cov: 33)
  • Exomes 𝑓: 0.53 (214398 hom.)
• Consequence: ITGA7 NM_002206.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.642
• Publications: 13 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: Labcorp Genetics (formerly Invitae), G2P, 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=-0.94).
• BP6: Variant 12-55703032-T-C is Benign according to our data. Variant chr12-55703032-T-C is described in ClinVar as Benign. ClinVar VariationId is 94044.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA7	NM_002206.3	MANE Select	c.334+19A>G		intron	N/A	NP_002197.2	Q13683-7
	ITGA7	NM_001410977.1		c.334+19A>G		intron	N/A	NP_001397906.1	Q13683-1
	ITGA7	NM_001144996.2		c.334+19A>G		intron	N/A	NP_001138468.1	Q13683-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA7	ENST00000257879.11	TSL:1 MANE Select	c.334+19A>G		intron	N/A	ENSP00000257879.7	Q13683-7
	ITGA7	ENST00000553804.6	TSL:1	c.334+19A>G		intron	N/A	ENSP00000452120.1	Q13683-3
	ITGA7	ENST00000555728.5	TSL:5	c.334+19A>G		intron	N/A	ENSP00000452387.1	Q13683-1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77558 AN: 151962 Hom.: 20959 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.490

GnomAD2 exomes AF: 0.596 AC: 149770 AN: 251112 AF XY: 0.597

Gnomad AFR exome AF: 0.362

Gnomad AMR exome AF: 0.716

Gnomad ASJ exome AF: 0.474

Gnomad EAS exome AF: 0.939

Gnomad FIN exome AF: 0.650

Gnomad NFE exome AF: 0.513

Gnomad OTH exome AF: 0.553

GnomAD4 exome AF: 0.532 AC: 777442 AN: 1461596 Hom.: 214398 Cov.: 57 AF XY: 0.537 AC XY: 390214 AN XY: 727110

African (AFR) AF: 0.353 AC: 11815 AN: 33476

American (AMR) AF: 0.703 AC: 31446 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 12535 AN: 26136

East Asian (EAS) AF: 0.936 AC: 37145 AN: 39700

South Asian (SAS) AF: 0.696 AC: 60020 AN: 86254

European-Finnish (FIN) AF: 0.641 AC: 34125 AN: 53204

Middle Eastern (MID) AF: 0.501 AC: 2890 AN: 5768

European-Non Finnish (NFE) AF: 0.499 AC: 555248 AN: 1111944

Other (OTH) AF: 0.533 AC: 32218 AN: 60390

GnomAD4 genome AF: 0.510 AC: 77605 AN: 152080 Hom.: 20973 Cov.: 33 AF XY: 0.524 AC XY: 38956 AN XY: 74324

African (AFR) AF: 0.364 AC: 15117 AN: 41500

American (AMR) AF: 0.606 AC: 9256 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1647 AN: 3470

East Asian (EAS) AF: 0.935 AC: 4804 AN: 5136

South Asian (SAS) AF: 0.717 AC: 3465 AN: 4832

European-Finnish (FIN) AF: 0.651 AC: 6892 AN: 10580

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34716 AN: 67962

Other (OTH) AF: 0.494 AC: 1044 AN: 2112

Alfa AF: 0.433 Hom.: 2626

Bravo AF: 0.497

Asia WGS AF: 0.768 AC: 2668 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Congenital muscular dystrophy due to integrin alpha-7 deficiency (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
DANN	Benign	0.37
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2293413;

hg19: chr12-56096816;