19-38894892-T-C

Position:

• chr19-38894892-T-C

Variant summary

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

The NM_012237.4(SIRT2):​c.64-1025A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 455,854 control chromosomes in the GnomAD database, including 97,140 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 0.67 (35380 hom., cov: 29)
  • Exomes 𝑓: 0.63 (61760 hom.)
• Consequence: SIRT2 NM_012237.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620

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]

SIRT2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRT2	NM_012237.4	c.64-1025A>G		intron_variant		ENST00000249396.12	NP_036369.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT2	ENST00000249396.12	c.64-1025A>G		intron_variant		1	NM_012237.4	ENSP00000249396.7

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101517 AN: 151724 Hom.: 35329 Cov.: 29

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.663

GnomAD3 exomes AF: 0.675 AC: 86843 AN: 128598 Hom.: 30478 AF XY: 0.669 AC XY: 47095 AN XY: 70352

Gnomad AFR exome AF: 0.835

Gnomad AMR exome AF: 0.753

Gnomad ASJ exome AF: 0.692

Gnomad EAS exome AF: 0.970

Gnomad SAS exome AF: 0.704

Gnomad FIN exome AF: 0.580

Gnomad NFE exome AF: 0.548

Gnomad OTH exome AF: 0.642

GnomAD4 exome AF: 0.626 AC: 190408 AN: 304012 Hom.: 61760 Cov.: 0 AF XY: 0.631 AC XY: 109223 AN XY: 173104

Gnomad4 AFR exome AF: 0.823

Gnomad4 AMR exome AF: 0.754

Gnomad4 ASJ exome AF: 0.692

Gnomad4 EAS exome AF: 0.972

Gnomad4 SAS exome AF: 0.700

Gnomad4 FIN exome AF: 0.581

Gnomad4 NFE exome AF: 0.544

Gnomad4 OTH exome AF: 0.632

GnomAD4 genome AF: 0.669 AC: 101624 AN: 151842 Hom.: 35380 Cov.: 29 AF XY: 0.677 AC XY: 50241 AN XY: 74214

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.967

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.666

Alfa AF: 0.582 Hom.: 36005

Bravo AF: 0.687

Asia WGS AF: 0.845 AC: 2935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.7
DANN	Benign	0.84

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: rs10410544; hg19: chr19-39385532;