12-55688893-G-C

Variant names:

• chr12-55688893-G-C
• rs201354330
• NM_002206.3:c.2909C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002206.3(ITGA7):​c.2909C>G​(p.Ala970Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A970T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ITGA7 NM_002206.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16691276).

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.2909C>G	p.Ala970Gly	missense	Exon 22 of 25	NP_002197.2
	ITGA7	NM_001410977.1		c.3041C>G	p.Ala1014Gly	missense	Exon 23 of 26	NP_001397906.1
	ITGA7	NM_001144996.2		c.2921C>G	p.Ala974Gly	missense	Exon 22 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.2909C>G	p.Ala970Gly	missense	Exon 22 of 25	ENSP00000257879.7
	ITGA7	ENST00000553804.6	TSL:1	c.2921C>G	p.Ala974Gly	missense	Exon 22 of 25	ENSP00000452120.1
	ITGA7	ENST00000555728.5	TSL:5	c.3041C>G	p.Ala1014Gly	missense	Exon 23 of 26	ENSP00000452387.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1461798 Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 31

Alfa AF: 0.00000646 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.52	N
PhyloP100		1.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.027
Sift	Benign	0.25	T
Sift4G	Benign	0.38	T
Polyphen		0.0010	B
Vest4		0.47
MutPred		0.45		Loss of stability (P = 0.0385)
MVP		0.25
MPC		0.17
ClinPred		0.053	T
GERP RS		0.21
Varity_R		0.037
gMVP		0.52
Mutation Taster		=93/7	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: rs201354330; hg19: chr12-56082677;