rs387907114

Positions:

• chr3-46995743-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_015175.3(NBEAL2):​c.1928A>T​(p.Glu643Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NBEAL2 NM_015175.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.14

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 Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856
• PP5: Variant 3-46995743-A-T is Pathogenic according to our data. Variant chr3-46995743-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 31119.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.1928A>T	p.Glu643Val	missense_variant	14/54	ENST00000450053.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBEAL2	ENST00000450053.8	c.1928A>T	p.Glu643Val	missense_variant	14/54	2	NM_015175.3	P2
NBEAL2	ENST00000416683.5	c.344A>T	p.Glu115Val	missense_variant	2/40	1
NBEAL2	ENST00000651747.1	c.1826A>T	p.Glu609Val	missense_variant	13/53			A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

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

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Pathogenic	0.79
Sift	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.49		Loss of disorder (P = 0.0402);
MVP		0.74
MPC		0.82
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.81
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs387907114; hg19: chr3-47037233;