rs9333289

Variant names:

• chr2-186633380-T-A
• rs9333289
• NM_002210.5:c.631+6T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-186633380-T-A
• chr2-186633380-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002210.5(ITGAV):​c.631+6T>A variant causes a splice region, intron 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ITGAV NM_002210.5 splice_region, intron
• Scores: Splicing: ADA: 0.6056
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675
• Publications: 18 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.631+6T>A		splice_region_variant, intron_variant	Intron 6 of 29	ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.524-2702T>A		intron_variant	Intron 4 of 27		NP_001138472.2
ITGAV	NM_001144999.3	c.493+6T>A		splice_region_variant, intron_variant	Intron 6 of 29		NP_001138471.2
ITGAV	XM_047444225.1	c.-213+6T>A		splice_region_variant, intron_variant	Intron 2 of 25		XP_047300181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.631+6T>A		splice_region_variant, intron_variant	Intron 6 of 29	1	NM_002210.5	ENSP00000261023.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1394266 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 696168

African (AFR) AF: 0.00 AC: 0 AN: 32538

American (AMR) AF: 0.00 AC: 0 AN: 43902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24888

East Asian (EAS) AF: 0.00 AC: 0 AN: 39122

South Asian (SAS) AF: 0.00 AC: 0 AN: 80856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5540

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1058642

Other (OTH) AF: 0.00 AC: 0 AN: 57572

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 14196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Benign	0.84
PhyloP100		0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.61
dbscSNV1_RF	Benign	0.50
SpliceAI score (max)		0.010		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: rs9333289; hg19: chr2-187498107;