rs2305637

Positions:

chr3-47004356-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015175.3(NBEAL2):c.6161C>T(p.Ser2054Phe) variant causes a missense change. The variant allele was found at a frequency of 0.164 in 1,602,398 control chromosomes in the GnomAD database, including 22,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1827 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21107 hom. )

Consequence

NBEAL2
NM_015175.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 5.90

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017380118).

BP6

Variant 3-47004356-C-T is Benign according to our data. Variant chr3-47004356-C-T is described in ClinVar as [Benign]. Clinvar id is 260587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-47004356-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 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.6161C>T	p.Ser2054Phe	missense_variant	37/54	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.6161C>T	p.Ser2054Phe	missense_variant	37/54	2	NM_015175.3	ENSP00000415034	P2	Q6ZNJ1-1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20874

AN:

151822

Hom.:

1826

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0409

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.0980

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.0929

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.160

GnomAD3 exomes

AF:

0.155

AC:

37011

AN:

239496

Hom.:

3274

AF XY:

0.154

AC XY:

19950

AN XY:

129628

show subpopulations

Gnomad AFR exome

AF:

0.0368

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.0980

Gnomad EAS exome

AF:

0.228

Gnomad SAS exome

AF:

0.0968

Gnomad FIN exome

AF:

0.237

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.166

AC:

241344

AN:

1450458

Hom.:

21107

Cov.:

AF XY:

0.164

AC XY:

118281

AN XY:

720286

show subpopulations

Gnomad4 AFR exome

AF:

0.0370

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.0914

Gnomad4 EAS exome

AF:

0.219

Gnomad4 SAS exome

AF:

0.0977

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.174

Gnomad4 OTH exome

AF:

0.156

GnomAD4 genome

AF:

0.137

AC:

20867

AN:

151940

Hom.:

1827

Cov.:

AF XY:

0.140

AC XY:

10385

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.0408

Gnomad4 AMR

AF:

0.150

Gnomad4 ASJ

AF:

0.0980

Gnomad4 EAS

AF:

0.224

Gnomad4 SAS

AF:

0.0927

Gnomad4 FIN

AF:

0.243

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.158

Hom.:

1885

Bravo

AF:

0.129

TwinsUK

AF:

0.177

AC:

655

ALSPAC

AF:

0.167

AC:

644

ESP6500AA

AF:

0.0466

AC:

185

ESP6500EA

AF:

0.168

AC:

1392

ExAC

AF:

0.151

AC:

18307

Asia WGS

AF:

0.165

AC:

576

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Gray platelet syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.4e-8

P;P;P

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-5.5

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

Polyphen

0.99

Vest4

0.26

MPC

1.4

ClinPred

0.036

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.83

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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