rs2224451

Positions:

• chr9-17636756-T-A
• chr9-17636756-T-C
• chr9-17636756-T-G

Variant summary

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

The NM_003026.5(SH3GL2):​c.45+57469T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,230 control chromosomes in the GnomAD database, including 63,675 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 0.90 (63675 hom., cov: 32)
• Consequence: SH3GL2 NM_003026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3GL2	NM_003026.5	c.45+57469T>A		intron_variant		ENST00000380607.5
SH3GL2	XM_011518005.4	c.147+18541T>A		intron_variant
SH3GL2	XM_047423730.1	c.-61+29502T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3GL2	ENST00000380607.5	c.45+57469T>A		intron_variant		1	NM_003026.5	P1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137447 AN: 152112 Hom.: 63631 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.971

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.935

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

GnomAD4 genome AF: 0.904 AC: 137549 AN: 152230 Hom.: 63675 Cov.: 32 AF XY: 0.907 AC XY: 67492 AN XY: 74436

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.961

Gnomad4 ASJ AF: 0.975

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.971

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.996

Gnomad4 OTH AF: 0.936

Alfa AF: 0.947 Hom.: 8090

Bravo AF: 0.891

Asia WGS AF: 0.973 AC: 3383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.1
DANN	Benign	0.69

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: rs2224451; hg19: chr9-17636754;