NM_015175.3:c.5413delG

Variant names:

• chr3-47002750-TG-T
• NM_015175.3:c.5413delG

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_015175.3(NBEAL2):​c.5413delG​(p.Ala1805ArgfsTer15) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000432 in 1,387,926 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: NBEAL2 NM_015175.3 frameshift
• Clinical Significance: Not reported in ClinVar
• 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 10 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEAL2	NM_015175.3	c.5413delG	p.Ala1805ArgfsTer15	frameshift_variant	Exon 33 of 54	ENST00000450053.8	NP_055990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBEAL2	ENST00000450053.8	c.5413delG	p.Ala1805ArgfsTer15	frameshift_variant	Exon 33 of 54	2	NM_015175.3	ENSP00000415034.2
NBEAL2	ENST00000416683.5	c.3274delG	p.Ala1092fs	frameshift_variant	Exon 19 of 40	1		ENSP00000410405.1
NBEAL2	ENST00000443829.5	c.517delG	p.Ala173fs	frameshift_variant	Exon 3 of 23	1		ENSP00000414560.1
NBEAL2	ENST00000651747.1	c.5311delG	p.Ala1771ArgfsTer15	frameshift_variant	Exon 32 of 53			ENSP00000499216.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000432 AC: 6 AN: 1387926 Hom.: 0 Cov.: 66 AF XY: 0.00000727 AC XY: 5 AN XY: 688152

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: 0.0000121

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.00000186

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: chr3-47044240;