rs74563314

Variant names:

• chr17-44376388-G-A
• NM_000419.5:c.2268C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-44376388-G-A
• chr17-44376388-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000419.5(ITGA2B):​c.2268C>T​(p.Ser756Ser) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ITGA2B NM_000419.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.04525
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.22

Genes affected

ITGA2B (HGNC:6138): (integrin subunit alpha 2b) This gene encodes a member of the integrin alpha chain family of proteins. The encoded preproprotein is proteolytically processed to generate light and heavy chains that associate through disulfide linkages to form a subunit of the alpha-IIb/beta-3 integrin cell adhesion receptor. This receptor plays a crucial role in the blood coagulation system, by mediating platelet aggregation. Mutations in this gene are associated with platelet-type bleeding disorders, which are characterized by a failure of platelet aggregation, including Glanzmann thrombasthenia. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2B	NM_000419.5	c.2268C>T	p.Ser756Ser	splice_region_variant, synonymous_variant	Exon 23 of 30	ENST00000262407.6	NP_000410.2
ITGA2B	XM_011524749.2	c.2421C>T	p.Ser807Ser	splice_region_variant, synonymous_variant	Exon 23 of 29		XP_011523051.2
ITGA2B	XM_011524750.2	c.2421C>T	p.Ser807Ser	splice_region_variant, synonymous_variant	Exon 23 of 29		XP_011523052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2B	ENST00000262407.6	c.2268C>T	p.Ser756Ser	splice_region_variant, synonymous_variant	Exon 23 of 30	1	NM_000419.5	ENSP00000262407.5
ITGA2B	ENST00000648408.1	c.1698C>T	p.Ser566Ser	splice_region_variant, synonymous_variant	Exon 19 of 25			ENSP00000498119.1
ITGA2B	ENST00000592462.5	n.1063C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 12 of 15	5
ITGA2B	ENST00000587295.5	c.-205C>T		upstream_gene_variant		3		ENSP00000467269.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461870 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.045
dbscSNV1_RF	Benign	0.32
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-42453756;