rs11575003

Variant names:

• chr19-38897202-T-C
• rs11575003
• NM_012237.4:c.63+1177A>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.63+1177A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,114 control chromosomes in the GnomAD database, including 8,107 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 0.23 (8107 hom., cov: 32)
• Consequence: SIRT2 NM_012237.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 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.63+1177A>G		intron	N/A	NP_036369.2
	SIRT2	NM_030593.3		c.-49+2304A>G		intron	N/A	NP_085096.1	Q8IXJ6-2
	SIRT2	NM_001193286.2		c.-49+2304A>G		intron	N/A	NP_001180215.1	A0A0A0MRF5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT2	ENST00000249396.12	TSL:1 MANE Select	c.63+1177A>G		intron	N/A	ENSP00000249396.7	Q8IXJ6-1
	SIRT2	ENST00000392081.6	TSL:1	c.-49+2304A>G		intron	N/A	ENSP00000375931.2	Q8IXJ6-2
	SIRT2	ENST00000872149.1		c.63+1177A>G		intron	N/A	ENSP00000542208.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34584 AN: 151994 Hom.: 8087 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0944

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.0685

Gnomad OTH AF: 0.202

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.228 AC: 34643 AN: 152114 Hom.: 8107 Cov.: 32 AF XY: 0.224 AC XY: 16690 AN XY: 74368

African (AFR) AF: 0.604 AC: 25009 AN: 41424

American (AMR) AF: 0.114 AC: 1741 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 420 AN: 3472

East Asian (EAS) AF: 0.124 AC: 643 AN: 5180

South Asian (SAS) AF: 0.133 AC: 640 AN: 4828

European-Finnish (FIN) AF: 0.0944 AC: 1000 AN: 10598

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.0685 AC: 4661 AN: 68018

Other (OTH) AF: 0.200 AC: 421 AN: 2102

Alfa AF: 0.165 Hom.: 1482

Bravo AF: 0.244

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.56
PhyloP100		0.30
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: rs11575003; hg19: chr19-39387842;