SH3BP2 p.Asp181Glu

Variant names:

• chr4-2827631-C-A
• NM_001122681.2:c.543C>A
• SH3BP2 p.Asp181Glu

Your query was ambiguous. Multiple possible variants found:

• chr4-2827631-C-A
• chr4-2827631-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001122681.2(SH3BP2):​c.543C>A​(p.Asp181Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D181D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SH3BP2 NM_001122681.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585
• Publications: 0 publications found

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]

SH3BP2 Gene-Disease associations (from GenCC):

• cherubism

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26581943).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122681.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP2	NM_001122681.2	MANE Select	c.543C>A	p.Asp181Glu	missense	Exon 7 of 13	NP_001116153.1	A0A384N6E5
	SH3BP2	NM_001145856.2		c.714C>A	p.Asp238Glu	missense	Exon 7 of 13	NP_001139328.1	P78314-4
	SH3BP2	NM_001145855.2		c.627C>A	p.Asp209Glu	missense	Exon 7 of 13	NP_001139327.1	P78314-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP2	ENST00000503393.8	TSL:1 MANE Select	c.543C>A	p.Asp181Glu	missense	Exon 7 of 13	ENSP00000422168.3	P78314-1
	SH3BP2	ENST00000511747.6	TSL:1	c.714C>A	p.Asp238Glu	missense	Exon 7 of 13	ENSP00000424846.2	P78314-4
	SH3BP2	ENST00000356331.10	TSL:1	n.804C>A		non_coding_transcript_exon	Exon 7 of 13

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1447042 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 718168

African (AFR) AF: 0.00 AC: 0 AN: 33254

American (AMR) AF: 0.00 AC: 0 AN: 42804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25764

East Asian (EAS) AF: 0.00 AC: 0 AN: 39032

South Asian (SAS) AF: 0.00 AC: 0 AN: 83616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104830

Other (OTH) AF: 0.00 AC: 0 AN: 59796

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.0097
Eigen_PC	Benign	-0.050
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.50	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	0.56	D
MutationAssessor	Benign	1.8	L
PhyloP100		0.58
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.64	N
REVEL	Uncertain	0.42
Sift	Benign	0.33	T
Sift4G	Benign	0.22	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.034
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-2829358;