Genetic Variant NM_012237.4:c.*426A>C (chr19-38878729-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012237.4(SIRT2):c.*426A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 157,442 control chromosomes in the GnomAD database, including 17,579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17144 hom., cov: 33)

Exomes 𝑓: 0.39 ( 435 hom. )

Consequence

SIRT2
NM_012237.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.27

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-38878729-T-G is Benign according to our data. Variant chr19-38878729-T-G is described in ClinVar as [Benign]. Clinvar id is 1269273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT2	NM_012237.4 link	c.*426A>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000249396.12	NP_036369.2	Q8IXJ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT2	ENST00000249396 link	c.*426A>C		3_prime_UTR_variant	Exon 16 of 16	1	NM_012237.4	ENSP00000249396.7		Q8IXJ6-1

Frequencies

GnomAD3 genomes

AF:

0.468

AC:

71074

AN:

151938

Hom.:

17116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.574

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.488

Gnomad ASJ

AF:

0.484

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.490

Gnomad FIN

AF:

0.381

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.463

GnomAD4 exome

AF:

0.386

AC:

2078

AN:

5386

Hom.:

435

Cov.:

AF XY:

0.389

AC XY:

1106

AN XY:

2846

show subpopulations

Gnomad4 AFR exome

AF:

0.577

Gnomad4 AMR exome

AF:

0.536

Gnomad4 ASJ exome

AF:

0.432

Gnomad4 EAS exome

AF:

0.432

Gnomad4 SAS exome

AF:

0.424

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.366

Gnomad4 OTH exome

AF:

0.413

GnomAD4 genome

AF:

0.468

AC:

71157

AN:

152056

Hom.:

17144

Cov.:

AF XY:

0.468

AC XY:

34755

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.573

Gnomad4 AMR

AF:

0.488

Gnomad4 ASJ

AF:

0.484

Gnomad4 EAS

AF:

0.512

Gnomad4 SAS

AF:

0.490

Gnomad4 FIN

AF:

0.381

Gnomad4 NFE

AF:

0.408

Gnomad4 OTH

AF:

0.470

Alfa

AF:

0.426

Hom.:

23427

Bravo

AF:

0.481

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 18, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31214610) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.47

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over