chr19-38881604-C-G

Position:

• chr19-38881604-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRT2	NM_012237.4	c.632-113G>C		intron_variant		ENST00000249396.12	NP_036369.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT2	ENST00000249396.12	c.632-113G>C		intron_variant		1	NM_012237.4	ENSP00000249396.7

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

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.574

Gnomad4 ASJ exome AF: 0.412

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.394

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.391

Gnomad4 OTH exome AF: 0.396

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

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.406

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs2082435; hg19: chr19-39372244; COSMIC: COSV50876060; COSMIC: COSV50876060;