2-238256992-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_022817.3(PER2):c.1995G>A(p.Ser665Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0564 in 1,613,494 control chromosomes in the GnomAD database, including 3,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 311 hom., cov: 33)

Exomes 𝑓: 0.056 ( 2787 hom. )

Consequence

PER2
NM_022817.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.676

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

advanced sleep phase syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
advanced sleep phase syndrome 1
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

PER2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 2-238256992-C-T is Benign according to our data. Variant chr2-238256992-C-T is described in CliVar as Benign. Clinvar id is 1278506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238256992-C-T is described in CliVar as Benign. Clinvar id is 1278506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238256992-C-T is described in CliVar as Benign. Clinvar id is 1278506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238256992-C-T is described in CliVar as Benign. Clinvar id is 1278506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.676 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER2	NM_022817.3 link	c.1995G>A	p.Ser665Ser	synonymous_variant	Exon 17 of 23	ENST00000254657.8	NP_073728.1	O15055-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PER2	ENST00000254657.8 link	c.1995G>A	p.Ser665Ser	synonymous_variant	Exon 17 of 23	1	NM_022817.3	ENSP00000254657.3	O15055-1
PER2	ENST00000707129.1 link	c.1995G>A	p.Ser665Ser	synonymous_variant	Exon 17 of 23			ENSP00000516757.1	O15055-1
PER2	ENST00000707130.1 link	c.1995G>A	p.Ser665Ser	synonymous_variant	Exon 17 of 23			ENSP00000516758.1	O15055-1

Frequencies

GnomAD3 genomes

AF:

0.0594

AC:

9034

AN:

152158

Hom.:

312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0627

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0370

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.0985

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0504

Gnomad OTH

AF:

0.0483

GnomAD2 exomes

AF:

0.0607

AC:

15231

AN:

250958

AF XY:

0.0639

show subpopulations

Gnomad AFR exome

AF:

0.0658

Gnomad AMR exome

AF:

0.0211

Gnomad ASJ exome

AF:

0.0241

Gnomad EAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.0864

Gnomad NFE exome

AF:

0.0490

Gnomad OTH exome

AF:

0.0531

GnomAD4 exome

AF:

0.0561

AC:

81957

AN:

1461218

Hom.:

2787

Cov.:

AF XY:

0.0578

AC XY:

42051

AN XY:

726942

show subpopulations

African (AFR)

AF:

0.0644

AC:

2156

AN:

33474

American (AMR)

AF:

0.0238

AC:

1063

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0265

AC:

693

AN:

26134

East Asian (EAS)

AF:

0.113

AC:

4489

AN:

39700

South Asian (SAS)

AF:

0.113

AC:

9751

AN:

86242

European-Finnish (FIN)

AF:

0.0861

AC:

4559

AN:

52958

Middle Eastern (MID)

AF:

0.0609

AC:

351

AN:

5766

European-Non Finnish (NFE)

AF:

0.0498

AC:

55415

AN:

1111844

Other (OTH)

AF:

0.0576

AC:

3480

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

3902

7804

11706

15608

19510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2210

4420

6630

8840

11050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0593

AC:

9030

AN:

152276

Hom.:

311

Cov.:

AF XY:

0.0626

AC XY:

4662

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0626

AC:

2602

AN:

41568

American (AMR)

AF:

0.0369

AC:

565

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0277

AC:

AN:

3468

East Asian (EAS)

AF:

0.106

AC:

551

AN:

5182

South Asian (SAS)

AF:

0.126

AC:

606

AN:

4814

European-Finnish (FIN)

AF:

0.0985

AC:

1045

AN:

10612

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0504

AC:

3430

AN:

68000

Other (OTH)

AF:

0.0473

AC:

100

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

430

860

1289

1719

2149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0432

Hom.:

Bravo

AF:

0.0531

Asia WGS

AF:

0.103

AC:

359

AN:

3478

EpiCase

AF:

0.0490

EpiControl

AF:

0.0491

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 01, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.31

CADD

Benign

7.7

(source)

DANN

Benign

0.92

PhyloP100

0.68

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over