rs2082435

Variant names:

• chr19-38881604-C-G
• rs2082435
• NM_012237.4:c.632-113G>C

Variant summary

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

The NM_012237.4(SIRT2):​c.632-113G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 795,514 control chromosomes in the GnomAD database, including 63,689 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 0.38 (11482 hom., cov: 30)
  • Exomes 𝑓: 0.40 (52207 hom.)
• Consequence: SIRT2 NM_012237.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• Publications: 8 publications found

Genes affected

SIRT2 (HGNC:10886): (sirtuin 2) This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Several transcript variants are resulted from alternative splicing of this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012237.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT2	NM_012237.4	MANE Select	c.632-113G>C		intron	N/A	NP_036369.2
	SIRT2	NM_030593.3		c.521-113G>C		intron	N/A	NP_085096.1
	SIRT2	NM_001193286.2		c.521-113G>C		intron	N/A	NP_001180215.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT2	ENST00000249396.12	TSL:1 MANE Select	c.632-113G>C		intron	N/A	ENSP00000249396.7
	SIRT2	ENST00000392081.6	TSL:1	c.521-113G>C		intron	N/A	ENSP00000375931.2
	SIRT2	ENST00000462654.5	TSL:1	n.1403-113G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58360 AN: 151796 Hom.: 11467 Cov.: 30

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.396 AC: 254932 AN: 643600 Hom.: 52207 AF XY: 0.396 AC XY: 134981 AN XY: 340690

African (AFR) AF: 0.320 AC: 5551 AN: 17324

American (AMR) AF: 0.574 AC: 19466 AN: 33914

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 7751 AN: 18810

East Asian (EAS) AF: 0.282 AC: 9235 AN: 32722

South Asian (SAS) AF: 0.394 AC: 24273 AN: 61590

European-Finnish (FIN) AF: 0.405 AC: 19152 AN: 47258

Middle Eastern (MID) AF: 0.469 AC: 1957 AN: 4170

European-Non Finnish (NFE) AF: 0.391 AC: 154423 AN: 394660

Other (OTH) AF: 0.396 AC: 13124 AN: 33152

GnomAD4 genome AF: 0.385 AC: 58412 AN: 151914 Hom.: 11482 Cov.: 30 AF XY: 0.386 AC XY: 28681 AN XY: 74242

African (AFR) AF: 0.320 AC: 13269 AN: 41438

American (AMR) AF: 0.496 AC: 7559 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1384 AN: 3468

East Asian (EAS) AF: 0.335 AC: 1728 AN: 5158

South Asian (SAS) AF: 0.386 AC: 1855 AN: 4804

European-Finnish (FIN) AF: 0.393 AC: 4148 AN: 10548

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27132 AN: 67928

Other (OTH) AF: 0.406 AC: 859 AN: 2114

Alfa AF: 0.383 Hom.: 1436

Bravo AF: 0.390

Asia WGS AF: 0.402 AC: 1397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.43
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2082435; hg19: chr19-39372244; COSMIC: COSV50876060; COSMIC: COSV50876060;