chr2-172427936-A-C

Variant names:

• chr2-172427936-A-C
• rs138572695
• NM_001394928.1:c.148A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000210.4(ITGA6):​c.148A>C​(p.Met50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. M50V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITGA6 NM_000210.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92

Genes affected

ITGA6 (HGNC:6142): (integrin subunit alpha 6) The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 6 subunit. This subunit may associate with a beta 1 or beta 4 subunit to form an integrin that interacts with extracellular matrix proteins including members of the laminin family. The alpha 6 beta 4 integrin may promote tumorigenesis, while the alpha 6 beta 1 integrin may negatively regulate erbB2/HER2 signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ENSG00000226963 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA6	NM_001394928.1	c.148A>C	p.Met50Leu	missense_variant	Exon 1 of 26	ENST00000442250.6	NP_001381857.1
ITGA6	NM_000210.4	c.148A>C	p.Met50Leu	missense_variant	Exon 1 of 26	ENST00000684293.1	NP_000201.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000442250.6	c.148A>C	p.Met50Leu	missense_variant	Exon 1 of 26	5	NM_001394928.1	ENSP00000406694.1
ITGA6	ENST00000684293.1	c.148A>C	p.Met50Leu	missense_variant	Exon 1 of 26		NM_000210.4	ENSP00000508249.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.073	.;T;.;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Pathogenic	0.91	D
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.41	N;N;N;N
PhyloP100		2.9
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.24	N;N;N;N
REVEL	Uncertain	0.31
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.088	B;.;.;.
Vest4		0.34
MutPred		0.62		Gain of catalytic residue at M50 (P = 0.1018);Gain of catalytic residue at M50 (P = 0.1018);Gain of catalytic residue at M50 (P = 0.1018);Gain of catalytic residue at M50 (P = 0.1018);
MVP		0.62
MPC		0.42
ClinPred		0.59	D
GERP RS		4.2
PromoterAI		0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.75
Mutation Taster		=88/12	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

LitVar

Other links and lift over

dbSNP: rs138572695; hg19: chr2-173292664;