17-2377640-T-C

Variant names:

• chr17-2377640-T-C
• rs2429917
• NM_014853.3:c.2803-217T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014853.3(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 NM_014853.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SGSM2	NM_014853.3	c.2803-217T>C		intron_variant	Intron 21 of 23	ENST00000268989.8	NP_055668.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGSM2	ENST00000268989.8	c.2803-217T>C		intron_variant	Intron 21 of 23	1	NM_014853.3	ENSP00000268989.3

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

African (AFR) AF: 0.965 AC: 8363 AN: 8664

American (AMR) AF: 0.893 AC: 9854 AN: 11040

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 7579 AN: 9152

East Asian (EAS) AF: 1.00 AC: 20678 AN: 20680

South Asian (SAS) AF: 0.947 AC: 30367 AN: 32082

European-Finnish (FIN) AF: 0.819 AC: 14291 AN: 17444

Middle Eastern (MID) AF: 0.831 AC: 1115 AN: 1342

European-Non Finnish (NFE) AF: 0.803 AC: 144865 AN: 180480

Other (OTH) AF: 0.844 AC: 14560 AN: 17250

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

African (AFR) AF: 0.968 AC: 40159 AN: 41484

American (AMR) AF: 0.877 AC: 13399 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 2895 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5161 AN: 5168

South Asian (SAS) AF: 0.953 AC: 4593 AN: 4820

European-Finnish (FIN) AF: 0.828 AC: 8741 AN: 10554

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54545 AN: 67984

Other (OTH) AF: 0.847 AC: 1774 AN: 2094

Alfa AF: 0.820 Hom.: 86870

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
PhyloP100		0.15
PromoterAI		-0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2429917; hg19: chr17-2280934;