3-47002132-G-C

Variant names:

• chr3-47002132-G-C
• rs2305635
• NM_015175.3:c.4995G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015175.3(NBEAL2):​c.4995G>C​(p.Val1665Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V1665V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: NBEAL2 NM_015175.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438
• Publications: 20 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.027).
• BP7: Synonymous conserved (PhyloP=0.438 with no splicing effect.

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.4995G>C	p.Val1665Val	synonymous	Exon 31 of 54	NP_055990.1	Q6ZNJ1-1
	NBEAL2	NM_001365116.2		c.4893G>C	p.Val1631Val	synonymous	Exon 30 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.4995G>C	p.Val1665Val	synonymous	Exon 31 of 54	ENSP00000415034.2	Q6ZNJ1-1
	NBEAL2	ENST00000416683.5	TSL:1	c.2856G>C	p.Val952Val	synonymous	Exon 17 of 40	ENSP00000410405.1	H0Y764
	NBEAL2	ENST00000443829.5	TSL:1	c.99G>C	p.Val33Val	synonymous	Exon 1 of 23	ENSP00000414560.1	H7C3Y7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 7385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.0
DANN	Benign	0.62
PhyloP100		0.44
PromoterAI		0.0042	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2305635; hg19: chr3-47043622;