rs2224957

Positions:

• chr9-17727221-A-G

Variant summary

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

The NM_003026.5(SH3GL2):​c.46-19845A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,070 control chromosomes in the GnomAD database, including 8,066 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 0.30 (8066 hom., cov: 33)
• Consequence: SH3GL2 NM_003026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3GL2	NM_003026.5	c.46-19845A>G		intron_variant		ENST00000380607.5	NP_003017.1
SH3GL2	XM_011518005.4	c.148-19845A>G		intron_variant			XP_011516307.1
SH3GL2	XM_047423730.1	c.-60-19845A>G		intron_variant			XP_047279686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3GL2	ENST00000380607.5	c.46-19845A>G		intron_variant		1	NM_003026.5	ENSP00000369981	P1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44942 AN: 151950 Hom.: 8024 Cov.: 33

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.296 AC: 45053 AN: 152070 Hom.: 8066 Cov.: 33 AF XY: 0.299 AC XY: 22251 AN XY: 74336

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.267

Alfa AF: 0.227 Hom.: 2285

Bravo AF: 0.313

Asia WGS AF: 0.309 AC: 1073 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	1.7
DANN	Benign	0.31

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: rs2224957; hg19: chr9-17727219;