rs2305635

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015175.3(NBEAL2):c.4995G>A(p.Val1665=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,550,500 control chromosomes in the GnomAD database, including 119,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9563 hom., cov: 34)

Exomes 𝑓: 0.39 ( 109867 hom. )

Consequence

NBEAL2
NM_015175.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.438

Variant links:

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]

NBEAL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 3-47002132-G-A is Benign according to our data. Variant chr3-47002132-G-A is described in ClinVar as [Benign]. Clinvar id is 260583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-47002132-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.438 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBEAL2	NM_015175.3 linkuse as main transcript	c.4995G>A	p.Val1665=	synonymous_variant	31/54	ENST00000450053.8	NP_055990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBEAL2	ENST00000450053.8 linkuse as main transcript	c.4995G>A	p.Val1665=	synonymous_variant	31/54	2	NM_015175.3	ENSP00000415034	P2	Q6ZNJ1-1
NBEAL2	ENST00000416683.5 linkuse as main transcript	c.2859G>A	p.Val953=	synonymous_variant	17/40	1		ENSP00000410405
NBEAL2	ENST00000443829.5 linkuse as main transcript	c.102G>A	p.Val34=	synonymous_variant	1/23	1		ENSP00000414560
NBEAL2	ENST00000651747.1 linkuse as main transcript	c.4893G>A	p.Val1631=	synonymous_variant	30/53			ENSP00000499216	A2

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52658

AN:

152012

Hom.:

9565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.240

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.314

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.401

Gnomad OTH

AF:

0.373

GnomAD3 exomes

AF:

0.364

AC:

55393

AN:

152366

Hom.:

10592

AF XY:

0.374

AC XY:

30402

AN XY:

81324

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.318

Gnomad SAS exome

AF:

0.411

Gnomad FIN exome

AF:

0.367

Gnomad NFE exome

AF:

0.410

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.393

AC:

549865

AN:

1398370

Hom.:

109867

Cov.:

AF XY:

0.395

AC XY:

272732

AN XY:

689836

show subpopulations

Gnomad4 AFR exome

AF:

0.237

Gnomad4 AMR exome

AF:

0.270

Gnomad4 ASJ exome

AF:

0.410

Gnomad4 EAS exome

AF:

0.290

Gnomad4 SAS exome

AF:

0.407

Gnomad4 FIN exome

AF:

0.375

Gnomad4 NFE exome

AF:

0.404

Gnomad4 OTH exome

AF:

0.391

GnomAD4 genome

AF:

0.346

AC:

52654

AN:

152130

Hom.:

9563

Cov.:

AF XY:

0.348

AC XY:

25921

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.240

Gnomad4 AMR

AF:

0.335

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.313

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.370

Gnomad4 NFE

AF:

0.401

Gnomad4 OTH

AF:

0.372

Alfa

AF:

0.380

Hom.:

6568

Bravo

AF:

0.335

Asia WGS

AF:

0.311

AC:

1086

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Gray platelet syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.1

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over