rs374312429

Variant names:

• chr3-47008311-G-A
• rs374312429
• NM_015175.3:c.7748G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-47008311-G-A
• chr3-47008311-G-C
• chr3-47008311-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015175.3(NBEAL2):​c.7748G>A​(p.Arg2583His) variant causes a missense change. The variant allele was found at a frequency of 0.0000335 in 1,612,976 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2583C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: NBEAL2 NM_015175.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.28
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.7748G>A	p.Arg2583His	missense	Exon 51 of 54	NP_055990.1	Q6ZNJ1-1
	NBEAL2	NM_001365116.2		c.7646G>A	p.Arg2549His	missense	Exon 50 of 53	NP_001352045.1	A0A494C1V1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEAL2	ENST00000450053.8	TSL:2 MANE Select	c.7748G>A	p.Arg2583His	missense	Exon 51 of 54	ENSP00000415034.2	Q6ZNJ1-1
	NBEAL2	ENST00000416683.5	TSL:1	c.5609G>A	p.Arg1870His	missense	Exon 37 of 40	ENSP00000410405.1	H0Y764
	NBEAL2	ENST00000443829.5	TSL:1	c.2762G>A	p.Arg921His	missense	Exon 20 of 23	ENSP00000414560.1	H7C3Y7

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000567 AC: 14 AN: 246746 AF XY: 0.0000597

Gnomad AFR exome AF: 0.000132

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000448

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.0000356 AC: 52 AN: 1460744 Hom.: 0 Cov.: 33 AF XY: 0.0000399 AC XY: 29 AN XY: 726550

African (AFR) AF: 0.000239 AC: 8 AN: 33472

American (AMR) AF: 0.000112 AC: 5 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39668

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1111416

Other (OTH) AF: 0.0000497 AC: 3 AN: 60346

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152232 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74366

African (AFR) AF: 0.0000241 AC: 1 AN: 41452

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000562 Hom.: 0

Bravo AF: 0.0000756

ESP6500AA AF: 0.000250 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.21
Sift	Uncertain	0.0080	D
Polyphen		0.65	P
Vest4		0.63
MVP		0.36
MPC		1.1
ClinPred		0.56	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.34
gMVP		0.39
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs374312429; hg19: chr3-47049801;