chr19-38894892-T-C

Variant names:

• chr19-38894892-T-C
• rs10410544
• NM_012237.4:c.64-1025A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 49 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]

ENSG00000305081 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT2	NM_012237.4	MANE Select	c.64-1025A>G		intron	N/A	NP_036369.2
	SIRT2	NM_030593.3		c.-48-1025A>G		intron	N/A	NP_085096.1
	SIRT2	NM_001193286.2		c.-48-1025A>G		intron	N/A	NP_001180215.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT2	ENST00000249396.12	TSL:1 MANE Select	c.64-1025A>G		intron	N/A	ENSP00000249396.7
	SIRT2	ENST00000392081.6	TSL:1	c.-48-1025A>G		intron	N/A	ENSP00000375931.2
	SIRT2	ENST00000414941.5	TSL:5	c.-48-1025A>G		intron	N/A	ENSP00000404309.1

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

GnomAD2 exomes AF: 0.675 AC: 86843 AN: 128598 AF XY: 0.669

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 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

African (AFR) AF: 0.823 AC: 7104 AN: 8628

American (AMR) AF: 0.754 AC: 20571 AN: 27280

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 7469 AN: 10790

East Asian (EAS) AF: 0.972 AC: 8948 AN: 9210

South Asian (SAS) AF: 0.700 AC: 41801 AN: 59742

European-Finnish (FIN) AF: 0.581 AC: 7197 AN: 12390

Middle Eastern (MID) AF: 0.672 AC: 1870 AN: 2782

European-Non Finnish (NFE) AF: 0.544 AC: 86449 AN: 158942

Other (OTH) AF: 0.632 AC: 8999 AN: 14248

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

African (AFR) AF: 0.828 AC: 34263 AN: 41394

American (AMR) AF: 0.732 AC: 11161 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2376 AN: 3470

East Asian (EAS) AF: 0.967 AC: 4971 AN: 5142

South Asian (SAS) AF: 0.717 AC: 3443 AN: 4800

European-Finnish (FIN) AF: 0.605 AC: 6392 AN: 10562

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36912 AN: 67908

Other (OTH) AF: 0.666 AC: 1405 AN: 2110

Alfa AF: 0.591 Hom.: 46269

Bravo AF: 0.687

Asia WGS AF: 0.845 AC: 2935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.7
DANN	Benign	0.84
PhyloP100		0.62
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: rs10410544; hg19: chr19-39385532;