19-38878995-G-T

Variant names:

• chr19-38878995-G-T
• rs45592833
• ENST00000462654.5:n.2101C>A

Variant summary

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

The ENST00000462654.5(SIRT2):​n.2101C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 675,324 control chromosomes in the GnomAD database, including 451 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 0.039 (333 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (118 hom.)
• Consequence: SIRT2 ENST00000462654.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000462654.5. 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.*160C>A		3_prime_UTR	Exon 16 of 16	NP_036369.2
	SIRT2	NR_034146.1		n.1555C>A		non_coding_transcript_exon	Exon 14 of 14
	SIRT2	NM_030593.3		c.*160C>A		3_prime_UTR	Exon 15 of 15	NP_085096.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT2	ENST00000462654.5	TSL:1	n.2101C>A		non_coding_transcript_exon	Exon 13 of 13
	SIRT2	ENST00000249396.12	TSL:1 MANE Select	c.*160C>A		3_prime_UTR	Exon 16 of 16	ENSP00000249396.7
	SIRT2	ENST00000392081.6	TSL:1	c.*160C>A		3_prime_UTR	Exon 15 of 15	ENSP00000375931.2

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5962 AN: 151936 Hom.: 327 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.00892

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.00784 AC: 4100 AN: 523270 Hom.: 118 Cov.: 7 AF XY: 0.00763 AC XY: 2068 AN XY: 271078

African (AFR) AF: 0.127 AC: 1597 AN: 12598

American (AMR) AF: 0.0133 AC: 179 AN: 13434

Ashkenazi Jewish (ASJ) AF: 0.00573 AC: 78 AN: 13602

East Asian (EAS) AF: 0.00630 AC: 177 AN: 28084

South Asian (SAS) AF: 0.00809 AC: 320 AN: 39540

European-Finnish (FIN) AF: 0.00245 AC: 78 AN: 31860

Middle Eastern (MID) AF: 0.0178 AC: 37 AN: 2074

European-Non Finnish (NFE) AF: 0.00340 AC: 1205 AN: 353954

Other (OTH) AF: 0.0153 AC: 429 AN: 28124

GnomAD4 genome AF: 0.0394 AC: 5987 AN: 152054 Hom.: 333 Cov.: 32 AF XY: 0.0371 AC XY: 2760 AN XY: 74356

African (AFR) AF: 0.128 AC: 5290 AN: 41444

American (AMR) AF: 0.0180 AC: 275 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3472

East Asian (EAS) AF: 0.0101 AC: 52 AN: 5166

South Asian (SAS) AF: 0.00934 AC: 45 AN: 4818

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10602

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.00297 AC: 202 AN: 67948

Other (OTH) AF: 0.0369 AC: 78 AN: 2114

Alfa AF: 0.0244 Hom.: 26

Bravo AF: 0.0448

Asia WGS AF: 0.0320 AC: 113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.51
PhyloP100		0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs45592833; hg19: chr19-39369635;