chr17-44372396-G-C

Variant names:

• chr17-44372396-G-C
• NM_000419.5:c.3088C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_000419.5(ITGA2B):​c.3088C>G​(p.Pro1030Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1030S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ITGA2B NM_000419.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.58

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 4 ACMG points.

• PM1: In a chain Integrin alpha-IIb light chain, form 1 (size 148) in uniprot entity ITA2B_HUMAN there are 8 pathogenic changes around while only 2 benign (80%) in NM_000419.5
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2B	NM_000419.5	c.3088C>G	p.Pro1030Ala	missense_variant	Exon 30 of 30	ENST00000262407.6	NP_000410.2
ITGA2B	XM_011524749.2	c.3139C>G	p.Pro1047Ala	missense_variant	Exon 29 of 29		XP_011523051.2
ITGA2B	XM_011524750.2	c.3124C>G	p.Pro1042Ala	missense_variant	Exon 29 of 29		XP_011523052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2B	ENST00000262407.6	c.3088C>G	p.Pro1030Ala	missense_variant	Exon 30 of 30	1	NM_000419.5	ENSP00000262407.5
ITGA2B	ENST00000648408.1	c.2401C>G	p.Pro801Ala	missense_variant	Exon 25 of 25			ENSP00000498119.1
ITGA2B	ENST00000587295.5	c.280C>G	p.Pro94Ala	missense_variant	Exon 3 of 3	3		ENSP00000467269.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 30 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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.26
MutPred		0.56		Loss of catalytic residue at P1029 (P = 0.0131);
MVP		0.83
MPC		0.94
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.29
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-42449764;