3-47002750-TG-TGG
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The ENST00000450053.8(NBEAL2):c.5413dupG(p.Ala1805GlyfsTer59) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,387,934 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000029 ( 0 hom. )
Consequence
NBEAL2
ENST00000450053.8 frameshift
ENST00000450053.8 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.53
Publications
3 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 syndromeInheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 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 3-47002750-T-TG is Pathogenic according to our data. Variant chr3-47002750-T-TG is described in ClinVar as Pathogenic. ClinVar VariationId is 31122.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000450053.8. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NBEAL2 | NM_015175.3 | MANE Select | c.5413dupG | p.Ala1805GlyfsTer59 | frameshift | Exon 33 of 54 | NP_055990.1 | ||
| NBEAL2 | NM_001365116.2 | c.5311dupG | p.Ala1771GlyfsTer59 | frameshift | Exon 32 of 53 | NP_001352045.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NBEAL2 | ENST00000450053.8 | TSL:2 MANE Select | c.5413dupG | p.Ala1805GlyfsTer59 | frameshift | Exon 33 of 54 | ENSP00000415034.2 | ||
| NBEAL2 | ENST00000416683.5 | TSL:1 | c.3274dupG | p.Ala1092fs | frameshift | Exon 19 of 40 | ENSP00000410405.1 | ||
| NBEAL2 | ENST00000443829.5 | TSL:1 | c.517dupG | p.Ala173fs | frameshift | Exon 3 of 23 | ENSP00000414560.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.0000107 AC: 2AN: 186074 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
186074
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
AF:
Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000288 AC: 4AN: 1387934Hom.: 0 Cov.: 66 AF XY: 0.00000436 AC XY: 3AN XY: 688150 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1387934
Hom.:
Cov.:
66
AF XY:
AC XY:
3
AN XY:
688150
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31852
American (AMR)
AF:
AC:
0
AN:
38710
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24068
East Asian (EAS)
AF:
AC:
0
AN:
35124
South Asian (SAS)
AF:
AC:
2
AN:
82644
European-Finnish (FIN)
AF:
AC:
0
AN:
40040
Middle Eastern (MID)
AF:
AC:
0
AN:
5054
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1073896
Other (OTH)
AF:
AC:
0
AN:
56546
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Gray platelet syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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