chr17-44372214-G-T

Variant names:

• chr17-44372214-G-T
• rs77992265
• NM_000419.5:c.*150C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_000419.5(ITGA2B):​c.*150C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000865 in 734,916 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00073 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00090 (1 hom.)
• Consequence: ITGA2B NM_000419.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0140
• Publications: 1 publications found

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]

ITGA2B Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 16

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• Glanzmann thrombasthenia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Glanzmann's thrombasthenia

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• Glanzmann thrombasthenia 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal dominant macrothrombocytopenia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-44372214-G-T is Benign according to our data. Variant chr17-44372214-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 323540.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000729 (111/152250) while in subpopulation EAS AF = 0.0143 (74/5182). AF 95% confidence interval is 0.0117. There are 1 homozygotes in GnomAd4. There are 65 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000419.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2B	NM_000419.5	MANE Select	c.*150C>A		3_prime_UTR	Exon 30 of 30	NP_000410.2	P08514-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2B	ENST00000262407.6	TSL:1 MANE Select	c.*150C>A		3_prime_UTR	Exon 30 of 30	ENSP00000262407.5	P08514-1
	ITGA2B	ENST00000901307.1		c.*150C>A		3_prime_UTR	Exon 29 of 29	ENSP00000571366.1
	ITGA2B	ENST00000949677.1		c.*150C>A		3_prime_UTR	Exon 29 of 29	ENSP00000619736.1

Frequencies

GnomAD3 genomes AF: 0.000730 AC: 111 AN: 152132 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0142

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000901 AC: 525 AN: 582666 Hom.: 1 Cov.: 7 AF XY: 0.000807 AC XY: 252 AN XY: 312406

African (AFR) AF: 0.000192 AC: 3 AN: 15594

American (AMR) AF: 0.000193 AC: 6 AN: 31044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19040

East Asian (EAS) AF: 0.0125 AC: 401 AN: 32046

South Asian (SAS) AF: 0.000404 AC: 25 AN: 61858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37450

Middle Eastern (MID) AF: 0.000375 AC: 1 AN: 2666

European-Non Finnish (NFE) AF: 0.000219 AC: 77 AN: 351952

Other (OTH) AF: 0.000387 AC: 12 AN: 31016

GnomAD4 genome AF: 0.000729 AC: 111 AN: 152250 Hom.: 1 Cov.: 31 AF XY: 0.000873 AC XY: 65 AN XY: 74428

African (AFR) AF: 0.000433 AC: 18 AN: 41542

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0143 AC: 74 AN: 5182

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000172 Hom.: 0

Bravo AF: 0.00110

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Glanzmann thrombasthenia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.49
PhyloP100		0.014
Mutation Taster		=100/0	polymorphism

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: rs77992265; hg19: chr17-42449582;