rs2305637

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP3BP4_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:8

Conservation

PhyloP100: 5.90

Publications

40 publications found

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 Gene-Disease associations (from GenCC):

gray platelet syndrome
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

NBEAL2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_015175.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, BayesDel_noAF, Cadd, Eigen, PROVEAN, REVEL, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

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 VariationId is 260587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015175.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEAL2	NM_015175.3	MANE Select	c.6161C>T	p.Ser2054Phe	missense	Exon 37 of 54	NP_055990.1	Q6ZNJ1-1
	NBEAL2	NM_001365116.2		c.6059C>T	p.Ser2020Phe	missense	Exon 36 of 53	NP_001352045.1	A0A494C1V1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NBEAL2	ENST00000450053.8	TSL:2 MANE Select	c.6161C>T	p.Ser2054Phe	missense	Exon 37 of 54	ENSP00000415034.2	Q6ZNJ1-1
NBEAL2	ENST00000416683.5	TSL:1	c.4022C>T	p.Ser1341Phe	missense	Exon 23 of 40	ENSP00000410405.1	H0Y764
NBEAL2	ENST00000443829.5	TSL:1	c.1265C>T	p.Ser422Phe	missense	Exon 7 of 23	ENSP00000414560.1	H7C3Y7

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

GnomAD2 exomes

AF:

0.155

AC:

37011

AN:

239496

AF XY:

0.154

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 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

African (AFR)

AF:

0.0370

AC:

1235

AN:

33338

American (AMR)

AF:

0.127

AC:

5638

AN:

44270

Ashkenazi Jewish (ASJ)

AF:

0.0914

AC:

2308

AN:

25250

East Asian (EAS)

AF:

0.219

AC:

8653

AN:

39594

South Asian (SAS)

AF:

0.0977

AC:

8271

AN:

84646

European-Finnish (FIN)

AF:

0.234

AC:

12318

AN:

52550

Middle Eastern (MID)

AF:

0.134

AC:

765

AN:

5720

European-Non Finnish (NFE)

AF:

0.174

AC:

192826

AN:

1105166

Other (OTH)

AF:

0.156

AC:

9330

AN:

59924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

12526

25052

37579

50105

62631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6740

13480

20220

26960

33700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.137

AC:

20867

AN:

151940

Hom.:

1827

Cov.:

AF XY:

0.140

AC XY:

10385

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.0408

AC:

1694

AN:

41470

American (AMR)

AF:

0.150

AC:

2288

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0980

AC:

340

AN:

3470

East Asian (EAS)

AF:

0.224

AC:

1151

AN:

5132

South Asian (SAS)

AF:

0.0927

AC:

446

AN:

4810

European-Finnish (FIN)

AF:

0.243

AC:

2561

AN:

10550

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.175

AC:

11867

AN:

67920

Other (OTH)

AF:

0.158

AC:

334

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

874

1749

2623

3498

4372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.157

Hom.:

2346

Bravo

AF:

0.129

Asia WGS

AF:

0.165

AC:

576

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (3)

Gray platelet syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

(source)

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

PhyloP100

5.9

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-5.5

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.83

gMVP

0.76

Mutation Taster

=81/19

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over