2-172491230-G-T

Position:

• chr2-172491230-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394928.1(ITGA6):​c.2905G>T​(p.Val969Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGA6 NM_001394928.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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]

PDK1-AS1 (HGNC:40441): (PDK1 and ITGA6 antisense RNA 1)

LOC124900513 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053836048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA6	NM_001394928.1	c.2905G>T	p.Val969Leu	missense_variant	23/26	ENST00000442250.6	NP_001381857.1
ITGA6	NM_000210.4	c.2788G>T	p.Val930Leu	missense_variant	22/26	ENST00000684293.1	NP_000201.2
LOC124900513	XR_007087304.1	n.703+4145C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000442250.6	c.2905G>T	p.Val969Leu	missense_variant	23/26	5	NM_001394928.1	ENSP00000406694
ITGA6	ENST00000684293.1	c.2788G>T	p.Val930Leu	missense_variant	22/26		NM_000210.4	ENSP00000508249	P3
PDK1-AS1	ENST00000442417.5	n.768+4145C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	10
DANN	Benign	0.93
DEOGEN2	Benign	0.050	.;.;T;.;.;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.69	T;T;T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.054	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.22	.;.;N;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.30	N;N;N;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.34	T;T;T;T;T;T
Sift4G	Benign	0.56	T;T;T;T;T;T
Polyphen		0.0	.;B;.;.;.;.
Vest4		0.18
MVP		0.33
MPC		0.39
ClinPred		0.057	T
GERP RS		2.0
Varity_R		0.028
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10209072; hg19: chr2-173355958;