2-186635955-A-G

Variant names:

• chr2-186635955-A-G
• rs3795865
• NM_002210.5:c.632-127A>G

Variant summary

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

The NM_002210.5(ITGAV):​c.632-127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 682,032 control chromosomes in the GnomAD database, including 37,244 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 0.28 (6832 hom., cov: 32)
  • Exomes 𝑓: 0.33 (30412 hom.)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 4 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.356 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.632-127A>G		intron	N/A	NP_002201.2
	ITGAV	NM_001145000.3		c.524-127A>G		intron	N/A	NP_001138472.2
	ITGAV	NM_001144999.3		c.494-127A>G		intron	N/A	NP_001138471.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAV	ENST00000261023.8	TSL:1 MANE Select	c.632-127A>G		intron	N/A	ENSP00000261023.3
	ITGAV	ENST00000374907.7	TSL:1	c.524-127A>G		intron	N/A	ENSP00000364042.3
	ITGAV	ENST00000696906.1		c.632-127A>G		intron	N/A	ENSP00000512967.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43203 AN: 151974 Hom.: 6834 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.329 AC: 174538 AN: 529940 Hom.: 30412 AF XY: 0.331 AC XY: 91567 AN XY: 276834

African (AFR) AF: 0.176 AC: 2220 AN: 12624

American (AMR) AF: 0.226 AC: 3621 AN: 16038

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 4656 AN: 13262

East Asian (EAS) AF: 0.0867 AC: 2578 AN: 29744

South Asian (SAS) AF: 0.324 AC: 12132 AN: 37400

European-Finnish (FIN) AF: 0.301 AC: 10329 AN: 34290

Middle Eastern (MID) AF: 0.415 AC: 962 AN: 2318

European-Non Finnish (NFE) AF: 0.362 AC: 129006 AN: 356718

Other (OTH) AF: 0.328 AC: 9034 AN: 27546

GnomAD4 genome AF: 0.284 AC: 43199 AN: 152092 Hom.: 6832 Cov.: 32 AF XY: 0.281 AC XY: 20865 AN XY: 74354

African (AFR) AF: 0.174 AC: 7228 AN: 41520

American (AMR) AF: 0.257 AC: 3930 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1226 AN: 3466

East Asian (EAS) AF: 0.0774 AC: 401 AN: 5182

South Asian (SAS) AF: 0.322 AC: 1552 AN: 4816

European-Finnish (FIN) AF: 0.305 AC: 3217 AN: 10562

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24458 AN: 67946

Other (OTH) AF: 0.298 AC: 630 AN: 2112

Alfa AF: 0.295 Hom.: 2172

Bravo AF: 0.275

Asia WGS AF: 0.215 AC: 747 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.3
DANN	Benign	0.62
PhyloP100		-0.060
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: rs3795865; hg19: chr2-187500682;