rs372277612
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_015175.3(NBEAL2):c.881C>G(p.Ser294Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
NBEAL2
NM_015175.3 stop_gained
NM_015175.3 stop_gained
Scores
2
2
3
Clinical Significance
Conservation
PhyloP100: 0.715
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-46991644-C-G is Pathogenic according to our data. Variant chr3-46991644-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 31117.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NBEAL2 | NM_015175.3 | c.881C>G | p.Ser294Ter | stop_gained | 8/54 | ENST00000450053.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NBEAL2 | ENST00000450053.8 | c.881C>G | p.Ser294Ter | stop_gained | 8/54 | 2 | NM_015175.3 | P2 | |
NBEAL2 | ENST00000651747.1 | c.860C>G | p.Ser287Ter | stop_gained | 8/53 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000422 AC: 1AN: 237148Hom.: 0 AF XY: 0.00000770 AC XY: 1AN XY: 129826
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GnomAD4 exome AF: 0.00000138 AC: 2AN: 1447260Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1AN XY: 720312
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GnomAD4 genome ? Cov.: 33
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Bravo
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ESP6500AA
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Gray platelet syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 17, 2011 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;A;N
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at