chr19-38878874-G-A

Variant names:

• chr19-38878874-G-A
• rs2241703
• ENST00000462654.5:n.2222C>T

Variant summary

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

The ENST00000462654.5(SIRT2):​n.2222C>T 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 0.0116 in 369,814 control chromosomes in the GnomAD database, including 384 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 0.0055 (40 hom., cov: 33)
  • Exomes 𝑓: 0.016 (344 hom.)
• Consequence: SIRT2 ENST00000462654.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.472
• Publications: 13 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 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.*281C>T		3_prime_UTR	Exon 16 of 16	NP_036369.2
	SIRT2	NR_034146.1		n.1676C>T		non_coding_transcript_exon	Exon 14 of 14
	SIRT2	NM_030593.3		c.*281C>T		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.2222C>T		non_coding_transcript_exon	Exon 13 of 13
	SIRT2	ENST00000249396.12	TSL:1 MANE Select	c.*281C>T		3_prime_UTR	Exon 16 of 16	ENSP00000249396.7
	SIRT2	ENST00000392081.6	TSL:1	c.*281C>T		3_prime_UTR	Exon 15 of 15	ENSP00000375931.2

Frequencies

GnomAD3 genomes AF: 0.00553 AC: 841 AN: 152216 Hom.: 40 Cov.: 33

Gnomad AFR AF: 0.000699

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00659

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00527

GnomAD4 exome AF: 0.0159 AC: 3448 AN: 217478 Hom.: 344 Cov.: 0 AF XY: 0.0148 AC XY: 1635 AN XY: 110350

African (AFR) AF: 0.000338 AC: 2 AN: 5920

American (AMR) AF: 0.00106 AC: 6 AN: 5652

Ashkenazi Jewish (ASJ) AF: 0.00457 AC: 37 AN: 8100

East Asian (EAS) AF: 0.192 AC: 3137 AN: 16330

South Asian (SAS) AF: 0.00173 AC: 17 AN: 9816

European-Finnish (FIN) AF: 0.00572 AC: 90 AN: 15736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1224

European-Non Finnish (NFE) AF: 0.000364 AC: 51 AN: 139982

Other (OTH) AF: 0.00734 AC: 108 AN: 14718

GnomAD4 genome AF: 0.00551 AC: 840 AN: 152336 Hom.: 40 Cov.: 33 AF XY: 0.00593 AC XY: 442 AN XY: 74486

African (AFR) AF: 0.000697 AC: 29 AN: 41598

American (AMR) AF: 0.00340 AC: 52 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.119 AC: 614 AN: 5162

South Asian (SAS) AF: 0.00476 AC: 23 AN: 4828

European-Finnish (FIN) AF: 0.00659 AC: 70 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68036

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.000414 Hom.: 2

Bravo AF: 0.00558

Asia WGS AF: 0.0390 AC: 137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.8
DANN	Benign	0.70
PhyloP100		0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2241703; hg19: chr19-39369514;