Variant rs2304670 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_022817.3(PER2):c.1992G>A(p.Ala664=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 1,613,452 control chromosomes in the GnomAD database, including 7,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.098 ( 776 hom., cov: 33)

Exomes 𝑓: 0.091 ( 6810 hom. )

Consequence

PER2
NM_022817.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.216

Variant links:

Genes affected

PER2 (HGNC:8846): (period circadian regulator 2) This gene is a member of the Period family of genes and is expressed in a circadian pattern in the suprachiasmatic nucleus, the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. This gene is upregulated by CLOCK/ARNTL heterodimers but then represses this upregulation in a feedback loop using PER/CRY heterodimers to interact with CLOCK/ARNTL. Polymorphisms in this gene may increase the risk of getting certain cancers and have been linked to sleep disorders. [provided by RefSeq, Jan 2014]

PER2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 2-238256995-C-T is Benign according to our data. Variant chr2-238256995-C-T is described in ClinVar as [Benign]. Clinvar id is 3055371.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.216 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PER2	NM_022817.3 linkuse as main transcript	c.1992G>A	p.Ala664=	synonymous_variant	17/23	ENST00000254657.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PER2	ENST00000254657.8 linkuse as main transcript	c.1992G>A	p.Ala664=	synonymous_variant	17/23	1	NM_022817.3	P1	O15055-1
PER2	ENST00000707129.1 linkuse as main transcript	c.1992G>A	p.Ala664=	synonymous_variant	17/23			P1
PER2	ENST00000707130.1 linkuse as main transcript	c.1992G>A	p.Ala664=	synonymous_variant	17/23			P1

Frequencies

GnomAD3 genomes

AF:

0.0977

AC:

14860

AN:

152152

Hom.:

776

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.0590

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.0580

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0906

Gnomad OTH

AF:

0.0923

GnomAD3 exomes

AF:

0.0974

AC:

24462

AN:

251084

Hom.:

1437

AF XY:

0.102

AC XY:

13805

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.0356

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.0535

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.0944

Gnomad OTH exome

AF:

0.0958

GnomAD4 exome

AF:

0.0914

AC:

133524

AN:

1461182

Hom.:

6810

Cov.:

AF XY:

0.0940

AC XY:

68339

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.0382

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.0585

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.163

Gnomad4 NFE exome

AF:

0.0857

Gnomad4 OTH exome

AF:

0.0969

GnomAD4 genome

AF:

0.0976

AC:

14868

AN:

152270

Hom.:

776

Cov.:

AF XY:

0.102

AC XY:

7600

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0589

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.0579

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.171

Gnomad4 NFE

AF:

0.0906

Gnomad4 OTH

AF:

0.0909

Alfa

AF:

0.0904

Hom.:

932

Bravo

AF:

0.0889

Asia WGS

AF:

0.0760

AC:

264

AN:

3478

EpiCase

AF:

0.0893

EpiControl

AF:

0.0886

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PER2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.91

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