3-46979842-G-GGCCGGA

Position:

• chr3-46979842-G-GGCCGGA

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_015175.3(NBEAL2):​c.-14_-9dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 441,060 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: NBEAL2 NM_015175.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25

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]

CCDC12 (HGNC:28332): (coiled-coil domain containing 12) Predicted to be part of U2-type spliceosomal complex and post-mRNA release spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00109 (165/151852) while in subpopulation AMR AF= 0.0036 (55/15262). AF 95% confidence interval is 0.00284. There are 1 homozygotes in gnomad4. There are 77 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBEAL2	NM_015175.3	c.-14_-9dup		5_prime_UTR_variant	1/54	ENST00000450053.8	NP_055990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBEAL2	ENST00000450053.8	c.-14_-9dup		5_prime_UTR_variant	1/54	2	NM_015175.3	ENSP00000415034	P2

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 165 AN: 151744 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00361

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0000956

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.000481

GnomAD3 exomes AF: 0.000565 AC: 12 AN: 21252 Hom.: 0 AF XY: 0.000831 AC XY: 11 AN XY: 13244

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000995

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00154

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000259

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00120 AC: 347 AN: 289208 Hom.: 1 Cov.: 0 AF XY: 0.00125 AC XY: 197 AN XY: 158018

Gnomad4 AFR exome AF: 0.000142

Gnomad4 AMR exome AF: 0.00225

Gnomad4 ASJ exome AF: 0.00343

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00390

Gnomad4 FIN exome AF: 0.000570

Gnomad4 NFE exome AF: 0.000986

Gnomad4 OTH exome AF: 0.00182

GnomAD4 genome AF: 0.00109 AC: 165 AN: 151852 Hom.: 1 Cov.: 33 AF XY: 0.00104 AC XY: 77 AN XY: 74258

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.00360

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0000956

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.000476

Alfa AF: 0.00135 Hom.: 0

Bravo AF: 0.00133

Asia WGS AF: 0.00117 AC: 4 AN: 3428

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Gray platelet syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs764010884; hg19: chr3-47021332;