rs2145656

chr9-17608786-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003026.5(SH3GL2):c.45+29499T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,168 control chromosomes in the GnomAD database, including 2,373 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2373 hom., cov: 33)
• Consequence: SH3GL2 NM_003026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.945

Genes affected

SH3GL2 (HGNC:10831): (SH3 domain containing GRB2 like 2, endophilin A1) Enables identical protein binding activity. Involved in negative regulation of blood-brain barrier permeability; negative regulation of gene expression; and negative regulation of protein phosphorylation. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3GL2	NM_003026.5	c.45+29499T>C		intron_variant		ENST00000380607.5
SH3GL2	XM_047423730.1	c.-61+1532T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3GL2	ENST00000380607.5	c.45+29499T>C		intron_variant		1	NM_003026.5	P1
SH3GL2	ENST00000467085.1	n.207-21568T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25782 AN: 152050 Hom.: 2376 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.170 AC: 25795 AN: 152168 Hom.: 2373 Cov.: 33 AF XY: 0.170 AC XY: 12672 AN XY: 74398

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.158

Alfa AF: 0.192 Hom.: 1787

Bravo AF: 0.165

Asia WGS AF: 0.262 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.3
Dann	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs2145656; hg19: chr9-17608784;