2-186678500-G-C

Variant names:

• chr2-186678500-G-C
• rs11902171
• NM_002210.5:c.*1208G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002210.5(ITGAV):​c.*1208G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 235,578 control chromosomes in the GnomAD database, including 6,494 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4076 hom., cov: 33)
  • Exomes 𝑓: 0.23 (2418 hom.)
• Consequence: ITGAV NM_002210.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468
• Publications: 25 publications found

Genes affected

ITGAV (HGNC:6150): (integrin subunit alpha V) The product of this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha subunit and a beta subunit that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha V subunit. This subunit associates with beta 1, beta 3, beta 5, beta 6 and beta 8 subunits. The heterodimer consisting of alpha V and beta 3 subunits is also known as the vitronectin receptor. This integrin may regulate angiogenesis and cancer progression. Alternative splicing results in multiple transcript variants. Note that the integrin alpha 5 and integrin alpha V subunits are encoded by distinct genes. [provided by RefSeq, Oct 2015]

ENSG00000227227 (HGNC:41242):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002210.5. 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
	ITGAV	NM_002210.5	MANE Select	c.*1208G>C		3_prime_UTR	Exon 30 of 30	NP_002201.2
	ITGAV	NM_001145000.3		c.*1208G>C		3_prime_UTR	Exon 28 of 28	NP_001138472.2
	ITGAV	NM_001144999.3		c.*1208G>C		3_prime_UTR	Exon 30 of 30	NP_001138471.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAV	ENST00000261023.8	TSL:1 MANE Select	c.*1208G>C		3_prime_UTR	Exon 30 of 30	ENSP00000261023.3
	ITGAV	ENST00000374907.7	TSL:1	c.*1208G>C		3_prime_UTR	Exon 28 of 28	ENSP00000364042.3
	ITGAV	ENST00000696908.1		n.*3765G>C		non_coding_transcript_exon	Exon 29 of 29	ENSP00000512969.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33883 AN: 151842 Hom.: 4074 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0776

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.230 AC: 19209 AN: 83618 Hom.: 2418 Cov.: 0 AF XY: 0.225 AC XY: 10393 AN XY: 46122

African (AFR) AF: 0.143 AC: 207 AN: 1452

American (AMR) AF: 0.194 AC: 644 AN: 3320

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 440 AN: 1924

East Asian (EAS) AF: 0.0714 AC: 228 AN: 3194

South Asian (SAS) AF: 0.195 AC: 2836 AN: 14528

European-Finnish (FIN) AF: 0.229 AC: 953 AN: 4168

Middle Eastern (MID) AF: 0.269 AC: 108 AN: 402

European-Non Finnish (NFE) AF: 0.253 AC: 12745 AN: 50306

Other (OTH) AF: 0.242 AC: 1048 AN: 4324

GnomAD4 genome AF: 0.223 AC: 33886 AN: 151960 Hom.: 4076 Cov.: 33 AF XY: 0.220 AC XY: 16330 AN XY: 74282

African (AFR) AF: 0.164 AC: 6814 AN: 41504

American (AMR) AF: 0.209 AC: 3194 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 896 AN: 3464

East Asian (EAS) AF: 0.0772 AC: 400 AN: 5180

South Asian (SAS) AF: 0.209 AC: 1007 AN: 4828

European-Finnish (FIN) AF: 0.227 AC: 2400 AN: 10584

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18231 AN: 67826

Other (OTH) AF: 0.242 AC: 510 AN: 2110

Alfa AF: 0.143 Hom.: 282

Bravo AF: 0.220

Asia WGS AF: 0.173 AC: 600 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.66
DANN	Benign	0.51
PhyloP100		-0.47
Mutation Taster		=100/0	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: rs11902171; hg19: chr2-187543227;