Variant 2-238257022-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022817.3(PER2):c.1965A>G(p.Ala655Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,613,266 control chromosomes in the GnomAD database, including 15,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1301 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13872 hom. )

Consequence

PER2
NM_022817.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.552

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-238257022-T-C is Benign according to our data. Variant chr2-238257022-T-C is described in ClinVar as [Benign]. Clinvar id is 1246724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.552 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER2	NM_022817.3 linkuse as main transcript	c.1965A>G	p.Ala655Ala	synonymous_variant	17/23	ENST00000254657.8	NP_073728.1	O15055-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PER2	ENST00000254657.8 linkuse as main transcript	c.1965A>G	p.Ala655Ala	synonymous_variant	17/23	1	NM_022817.3	ENSP00000254657.3	O15055-1
PER2	ENST00000707129.1 linkuse as main transcript	c.1965A>G	p.Ala655Ala	synonymous_variant	17/23			ENSP00000516757.1	O15055-1
PER2	ENST00000707130.1 linkuse as main transcript	c.1965A>G	p.Ala655Ala	synonymous_variant	17/23			ENSP00000516758.1	O15055-1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17350

AN:

152152

Hom.:

1301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0370

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.0885

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.0598

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.129

AC:

32495

AN:

250950

Hom.:

2373

AF XY:

0.125

AC XY:

16996

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.0328

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.0989

Gnomad EAS exome

AF:

0.107

Gnomad SAS exome

AF:

0.0531

Gnomad FIN exome

AF:

0.169

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.134

AC:

195981

AN:

1460996

Hom.:

13872

Cov.:

AF XY:

0.131

AC XY:

95391

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.0304

Gnomad4 AMR exome

AF:

0.196

Gnomad4 ASJ exome

AF:

0.0958

Gnomad4 EAS exome

AF:

0.120

Gnomad4 SAS exome

AF:

0.0533

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.114

AC:

17355

AN:

152270

Hom.:

1301

Cov.:

AF XY:

0.115

AC XY:

8531

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0369

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.0885

Gnomad4 EAS

AF:

0.117

Gnomad4 SAS

AF:

0.0600

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.131

Hom.:

2214

Bravo

AF:

0.112

Asia WGS

AF:

0.0760

AC:

263

AN:

3478

EpiCase

AF:

0.135

EpiControl

AF:

0.138

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 01, 2019	- -

PER2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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

-0.82

CADD

Benign

0.44

DANN

Benign

0.50

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