2-172487375-C-T

Variant names:

• chr2-172487375-C-T
• rs2293649
• NM_001394928.1:c.2199C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000210.4(ITGA6):​c.2082C>T​(p.Asp694Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,612,818 control chromosomes in the GnomAD database, including 54,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5321 hom., cov: 33)
  • Exomes 𝑓: 0.24 (49153 hom.)
• Consequence: ITGA6 NM_000210.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.04
• Publications: 23 publications found

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]

ITGA6-AS1 (HGNC:40308): (ITGA6 antisense RNA 1)

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 2-172487375-C-T is Benign according to our data. Variant chr2-172487375-C-T is described in ClinVar as Benign. ClinVar VariationId is 332369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000210.4. 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
	ITGA6	NM_001394928.1	MANE Plus Clinical	c.2199C>T	p.Asp733Asp	synonymous	Exon 16 of 26	NP_001381857.1	P23229-1
	ITGA6	NM_000210.4	MANE Select	c.2082C>T	p.Asp694Asp	synonymous	Exon 15 of 26	NP_000201.2	P23229-2
	ITGA6	NM_001079818.3		c.2082C>T	p.Asp694Asp	synonymous	Exon 15 of 25	NP_001073286.1	P23229-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA6	ENST00000442250.6	TSL:5 MANE Plus Clinical	c.2199C>T	p.Asp733Asp	synonymous	Exon 16 of 26	ENSP00000406694.1	P23229-1
	ITGA6	ENST00000684293.1	MANE Select	c.2082C>T	p.Asp694Asp	synonymous	Exon 15 of 26	ENSP00000508249.1	P23229-2
	ITGA6	ENST00000264107.12	TSL:1	c.2082C>T	p.Asp694Asp	synonymous	Exon 15 of 26	ENSP00000264107.8	A0A8C8KBL6

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38456 AN: 152008 Hom.: 5314 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.253

GnomAD2 exomes AF: 0.306 AC: 76760 AN: 251228 AF XY: 0.303

Gnomad AFR exome AF: 0.212

Gnomad AMR exome AF: 0.430

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.540

Gnomad FIN exome AF: 0.345

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.244 AC: 356353 AN: 1460692 Hom.: 49153 Cov.: 33 AF XY: 0.248 AC XY: 180531 AN XY: 726742

African (AFR) AF: 0.218 AC: 7309 AN: 33466

American (AMR) AF: 0.423 AC: 18897 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 6662 AN: 26130

East Asian (EAS) AF: 0.569 AC: 22601 AN: 39694

South Asian (SAS) AF: 0.406 AC: 35042 AN: 86216

European-Finnish (FIN) AF: 0.337 AC: 17992 AN: 53416

Middle Eastern (MID) AF: 0.253 AC: 1461 AN: 5766

European-Non Finnish (NFE) AF: 0.208 AC: 230591 AN: 1110956

Other (OTH) AF: 0.262 AC: 15798 AN: 60330

GnomAD4 genome AF: 0.253 AC: 38495 AN: 152126 Hom.: 5321 Cov.: 33 AF XY: 0.265 AC XY: 19687 AN XY: 74348

African (AFR) AF: 0.213 AC: 8829 AN: 41502

American (AMR) AF: 0.340 AC: 5191 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 887 AN: 3468

East Asian (EAS) AF: 0.551 AC: 2859 AN: 5188

South Asian (SAS) AF: 0.417 AC: 2011 AN: 4820

European-Finnish (FIN) AF: 0.352 AC: 3717 AN: 10556

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14203 AN: 67994

Other (OTH) AF: 0.257 AC: 542 AN: 2112

Alfa AF: 0.227 Hom.: 8293

Bravo AF: 0.252

Asia WGS AF: 0.475 AC: 1649 AN: 3478

EpiCase AF: 0.218

EpiControl AF: 0.209

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Junctional epidermolysis bullosa with pyloric atresia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.99
DANN	Benign	0.83
PhyloP100		-2.0
Mutation Taster		=99/1	polymorphism (auto)

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: rs2293649; hg19: chr2-173352103; COSMIC: COSV51219189; COSMIC: COSV51219189;