rs12938868

Variant names:

• chr17-44378349-G-A
• rs12938868
• NM_000419.5:c.2094+13C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000419.5(ITGA2B):​c.2094+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,607,138 control chromosomes in the GnomAD database, including 819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (93 hom., cov: 32)
  • Exomes 𝑓: 0.028 (726 hom.)
• Consequence: ITGA2B NM_000419.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.599

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-44378349-G-A is Benign according to our data. Variant chr17-44378349-G-A is described in ClinVar as [Benign]. Clinvar id is 256038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0229 (3483/152366) while in subpopulation NFE AF= 0.0293 (1996/68034). AF 95% confidence interval is 0.0283. There are 93 homozygotes in gnomad4. There are 1807 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 93 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2B	NM_000419.5	c.2094+13C>T		intron_variant	Intron 20 of 29	ENST00000262407.6	NP_000410.2
ITGA2B	XM_011524749.2	c.2247+13C>T		intron_variant	Intron 20 of 28		XP_011523051.2
ITGA2B	XM_011524750.2	c.2247+13C>T		intron_variant	Intron 20 of 28		XP_011523052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2B	ENST00000262407.6	c.2094+13C>T		intron_variant	Intron 20 of 29	1	NM_000419.5	ENSP00000262407.5
ITGA2B	ENST00000648408.1	c.1524+13C>T		intron_variant	Intron 16 of 24			ENSP00000498119.1
ITGA2B	ENST00000592462.5	n.889+13C>T		intron_variant	Intron 9 of 14	5

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3484 AN: 152248 Hom.: 94 Cov.: 32

Gnomad AFR AF: 0.00446

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.0786

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.0191

GnomAD3 exomes AF: 0.0261 AC: 6395 AN: 244964 Hom.: 140 AF XY: 0.0265 AC XY: 3518 AN XY: 132754

Gnomad AFR exome AF: 0.00437

Gnomad AMR exome AF: 0.0122

Gnomad ASJ exome AF: 0.0300

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.0104

Gnomad FIN exome AF: 0.0719

Gnomad NFE exome AF: 0.0327

Gnomad OTH exome AF: 0.0303

GnomAD4 exome AF: 0.0284 AC: 41329 AN: 1454772 Hom.: 726 Cov.: 32 AF XY: 0.0278 AC XY: 20066 AN XY: 722730

Gnomad4 AFR exome AF: 0.00459

Gnomad4 AMR exome AF: 0.0133

Gnomad4 ASJ exome AF: 0.0307

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.0751

Gnomad4 NFE exome AF: 0.0299

Gnomad4 OTH exome AF: 0.0258

GnomAD4 genome AF: 0.0229 AC: 3483 AN: 152366 Hom.: 93 Cov.: 32 AF XY: 0.0243 AC XY: 1807 AN XY: 74508

Gnomad4 AFR AF: 0.00445

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.0786

Gnomad4 NFE AF: 0.0293

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0273 Hom.: 18

Bravo AF: 0.0181

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Glanzmann thrombasthenia Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.45
DANN	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs12938868; hg19: chr17-42455717;