rs201015016
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_015175.3(NBEAL2):c.1038C>T(p.Tyr346=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 1,605,408 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0019 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0026 ( 7 hom. )
Consequence
NBEAL2
NM_015175.3 synonymous
NM_015175.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.12
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 3-46992480-C-T is Benign according to our data. Variant chr3-46992480-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 435924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46992480-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.12 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00193 (294/152116) while in subpopulation NFE AF= 0.00328 (223/67980). AF 95% confidence interval is 0.00293. There are 1 homozygotes in gnomad4. There are 129 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NBEAL2 | NM_015175.3 | c.1038C>T | p.Tyr346= | synonymous_variant | 10/54 | ENST00000450053.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NBEAL2 | ENST00000450053.8 | c.1038C>T | p.Tyr346= | synonymous_variant | 10/54 | 2 | NM_015175.3 | P2 | |
NBEAL2 | ENST00000651747.1 | c.1011+534C>T | intron_variant | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00193 AC: 294AN: 151998Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00191 AC: 446AN: 233492Hom.: 0 AF XY: 0.00183 AC XY: 233AN XY: 127122
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GnomAD4 exome AF: 0.00263 AC: 3822AN: 1453292Hom.: 7 Cov.: 32 AF XY: 0.00254 AC XY: 1834AN XY: 722144
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GnomAD4 genome ? AF: 0.00193 AC: 294AN: 152116Hom.: 1 Cov.: 33 AF XY: 0.00173 AC XY: 129AN XY: 74380
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 19, 2017 | - - |
NBEAL2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 24, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2018 | - - |
Gray platelet syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at