rs2209426

Positions:

• chr9-17766317-G-A
• chr9-17766317-G-C
• chr9-17766317-G-T

Variant summary

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

The NM_003026.5(SH3GL2):​c.187+4808G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,194 control chromosomes in the GnomAD database, including 51,155 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 0.82 (51155 hom., cov: 33)
• Consequence: SH3GL2 NM_003026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3GL2	NM_003026.5	c.187+4808G>A		intron_variant		ENST00000380607.5
SH3GL2	XM_011518005.4	c.289+4808G>A		intron_variant
SH3GL2	XM_047423730.1	c.82+4808G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3GL2	ENST00000380607.5	c.187+4808G>A		intron_variant		1	NM_003026.5	P1

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124331 AN: 152076 Hom.: 51118 Cov.: 33

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.818 AC: 124419 AN: 152194 Hom.: 51155 Cov.: 33 AF XY: 0.813 AC XY: 60467 AN XY: 74394

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.964

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.825

Alfa AF: 0.824 Hom.: 25290

Bravo AF: 0.815

Asia WGS AF: 0.840 AC: 2921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.61

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: rs2209426; hg19: chr9-17766315;