17-2377640-T-C

Position:

• chr17-2377640-T-C

Variant summary

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

The ENST00000268989.8(SGSM2):​c.2803-217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 450,188 control chromosomes in the GnomAD database, including 165,177 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 0.87 (58098 hom., cov: 30)
  • Exomes 𝑓: 0.84 (107079 hom.)
• Consequence: SGSM2 ENST00000268989.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

Genes affected

SGSM2 (HGNC:29026): (small G protein signaling modulator 2) The protein encoded by this gene is a GTPase activator with activity towards RAB32 and RAB33B, which are regulators of membrane trafficking. The encoded protein inactivates RAB32 and can bind RAB9A-GTP, a protein required for RAB32 activation. [provided by RefSeq, Oct 2016]

SGSM2-AS1 (HGNC:56091): (SGSM2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGSM2	NM_014853.3	c.2803-217T>C		intron_variant		ENST00000268989.8	NP_055668.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSM2	ENST00000268989.8	c.2803-217T>C		intron_variant		1	NM_014853.3	ENSP00000268989	P4
SGSM2-AS1	ENST00000574290.1	n.162-788A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132221 AN: 151936 Hom.: 58033 Cov.: 30

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.846

GnomAD4 exome AF: 0.844 AC: 251672 AN: 298134 Hom.: 107079 Cov.: 2 AF XY: 0.849 AC XY: 133770 AN XY: 157590

Gnomad4 AFR exome AF: 0.965

Gnomad4 AMR exome AF: 0.893

Gnomad4 ASJ exome AF: 0.828

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.947

Gnomad4 FIN exome AF: 0.819

Gnomad4 NFE exome AF: 0.803

Gnomad4 OTH exome AF: 0.844

GnomAD4 genome AF: 0.870 AC: 132345 AN: 152054 Hom.: 58098 Cov.: 30 AF XY: 0.874 AC XY: 64939 AN XY: 74330

Gnomad4 AFR AF: 0.968

Gnomad4 AMR AF: 0.877

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.847

Alfa AF: 0.816 Hom.: 65546

Bravo AF: 0.877

Asia WGS AF: 0.971 AC: 3374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.4
DANN	Benign	0.74

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: rs2429917; hg19: chr17-2280934;