2-186656533-C-T

Variant names:

• chr2-186656533-C-T
• rs3738919
• NM_002210.5:c.1719+132C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002210.5(ITGAV):​c.1719+132C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000201 in 497,348 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.1719+132C>T		intron_variant	Intron 17 of 29	ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.1611+132C>T		intron_variant	Intron 15 of 27		NP_001138472.2
ITGAV	NM_001144999.3	c.1581+132C>T		intron_variant	Intron 17 of 29		NP_001138471.2
ITGAV	XM_047444225.1	c.876+132C>T		intron_variant	Intron 13 of 25		XP_047300181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.1719+132C>T		intron_variant	Intron 17 of 29	1	NM_002210.5	ENSP00000261023.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000201 AC: 1 AN: 497348 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 256762

African (AFR) AF: 0.00 AC: 0 AN: 10708

American (AMR) AF: 0.00 AC: 0 AN: 10408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12966

East Asian (EAS) AF: 0.00 AC: 0 AN: 25628

South Asian (SAS) AF: 0.00 AC: 0 AN: 31622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2784

European-Non Finnish (NFE) AF: 0.00000297 AC: 1 AN: 337172

Other (OTH) AF: 0.00 AC: 0 AN: 27028

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.54
PhyloP100		-0.084

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: rs3738919; hg19: chr2-187521260;