chr12-55695573-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002206.3(ITGA7):​c.1952G>C​(p.Arg651Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R651H) has been classified as Benign.

Frequency

Genomes: not found (cov: 28)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ITGA7
NM_002206.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0920

Publications

56 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31641752).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITGA7NM_002206.3 linkc.1952G>C p.Arg651Pro missense_variant Exon 14 of 25 ENST00000257879.11 NP_002197.2 Q13683-7Q4LE35

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITGA7ENST00000257879.11 linkc.1952G>C p.Arg651Pro missense_variant Exon 14 of 25 1 NM_002206.3 ENSP00000257879.7 Q13683-7

Frequencies

GnomAD3 genomes
Cov.:
28
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461822
Hom.:
0
Cov.:
46
AF XY:
0.00
AC XY:
0
AN XY:
727210
show subpopulations
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:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111960
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
28
Alfa
AF:
0.00
Hom.:
93299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.050
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.019
.;.;T;.;T
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.73
FATHMM_MKL
Benign
0.16
N
LIST_S2
Uncertain
0.87
D;D;D;D;D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.32
T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.9
.;.;.;.;L
PhyloP100
0.092
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-2.2
N;N;N;N;N
REVEL
Benign
0.22
Sift
Benign
0.032
D;D;D;D;D
Sift4G
Benign
0.13
T;T;T;T;T
Polyphen
0.098
B;.;.;B;B
Vest4
0.42
MutPred
0.69
.;.;.;.;Gain of sheet (P = 0.0344);
MVP
0.39
MPC
0.43
ClinPred
0.35
T
GERP RS
-0.71
Varity_R
0.38
gMVP
0.76
Mutation Taster
=89/11
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

Publications

Other links and lift over

dbSNP: rs1800974; hg19: chr12-56089357; API