rs794726683

chr3-47002750-T-TG

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_015175.3(NBEAL2):c.5413dup(p.Ala1805GlyfsTer59) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,387,934 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: NBEAL2 NM_015175.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.53

Genes affected

NBEAL2 (HGNC:31928): (neurobeachin like 2) The protein encoded by this gene contains a beige and Chediak-Higashi (BEACH) domain and multiple WD40 domains, and may play a role in megakaryocyte alpha-granule biogenesis. Mutations in this gene are a cause of gray platelet syndrome. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-47002750-T-TG is Pathogenic according to our data. Variant chr3-47002750-T-TG is described in ClinVar as [Pathogenic]. Clinvar id is 31122.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBEAL2	NM_015175.3	c.5413dup	p.Ala1805GlyfsTer59	frameshift_variant	33/54	ENST00000450053.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBEAL2	ENST00000450053.8	c.5413dup	p.Ala1805GlyfsTer59	frameshift_variant	33/54	2	NM_015175.3	P2
NBEAL2	ENST00000416683.5	c.3276dup	p.Ala1093GlyfsTer59	frameshift_variant	19/40	1
NBEAL2	ENST00000443829.5	c.518dup	p.Ala174GlyfsTer59	frameshift_variant	3/23	1
NBEAL2	ENST00000651747.1	c.5311dup	p.Ala1771GlyfsTer59	frameshift_variant	32/53			A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000288 AC: 4 AN: 1387934 Hom.: 0 Cov.: 66 AF XY: 0.00000436 AC XY: 3 AN XY: 688150

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: 0.0000242

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000186

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Gray platelet syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 17, 2011

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs794726683; hg19: chr3-47044240;