rs190648042
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2
The NM_001122681.2(SH3BP2):āc.1686A>Gā(p.Ter562TrpextTer30) variant causes a stop lost change. The variant allele was found at a frequency of 0.000812 in 1,563,928 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00070 ( 1 hom., cov: 33)
Exomes š: 0.00082 ( 1 hom. )
Consequence
SH3BP2
NM_001122681.2 stop_lost
NM_001122681.2 stop_lost
Scores
2
1
4
Clinical Significance
Conservation
PhyloP100: 6.39
Genes affected
SH3BP2 (HGNC:10825): (SH3 domain binding protein 2) The protein encoded by this gene has an N-terminal pleckstrin homology (PH) domain, an SH3-binding proline-rich region, and a C-terminal SH2 domain. The protein binds to the SH3 domains of several proteins including the ABL1 and SYK protein tyrosine kinases , and functions as a cytoplasmic adaptor protein to positively regulate transcriptional activity in T, natural killer (NK), and basophilic cells. Mutations in this gene result in cherubism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PM4
?
Stoplost variant in NM_001122681.2 Downstream stopcodon found after 580 codons.
BP6
?
Variant 4-2833834-A-G is Benign according to our data. Variant chr4-2833834-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 525208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000696 (106/152288) while in subpopulation NFE AF= 0.00109 (74/68020). AF 95% confidence interval is 0.000888. There are 1 homozygotes in gnomad4. There are 55 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 106 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH3BP2 | NM_001122681.2 | c.1686A>G | p.Ter562TrpextTer30 | stop_lost | 13/13 | ENST00000503393.8 | |
SH3BP2 | NM_001145856.2 | c.1857A>G | p.Ter619TrpextTer30 | stop_lost | 13/13 | ||
SH3BP2 | NM_001145855.2 | c.1770A>G | p.Ter590TrpextTer30 | stop_lost | 13/13 | ||
SH3BP2 | NM_003023.4 | c.1686A>G | p.Ter562TrpextTer30 | stop_lost | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH3BP2 | ENST00000503393.8 | c.1686A>G | p.Ter562TrpextTer30 | stop_lost | 13/13 | 1 | NM_001122681.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000697 AC: 106AN: 152170Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000583 AC: 102AN: 175060Hom.: 0 AF XY: 0.000585 AC XY: 55AN XY: 94078
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GnomAD4 exome AF: 0.000825 AC: 1164AN: 1411640Hom.: 1 Cov.: 31 AF XY: 0.000791 AC XY: 552AN XY: 698222
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GnomAD4 genome ? AF: 0.000696 AC: 106AN: 152288Hom.: 1 Cov.: 33 AF XY: 0.000739 AC XY: 55AN XY: 74464
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fibrous dysplasia of jaw Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 03, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
N;N;N;N;N;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