Genetic Variant PER2:c.231-88A>C (chr2-238277281-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022817.3(PER2):c.231-88A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 882,020 control chromosomes in the GnomAD database, including 7,576 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 0.11 ( 1215 hom., cov: 32)

Exomes 𝑓: 0.13 ( 6361 hom. )

Consequence

PER2
NM_022817.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.412

Publications

21 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER2	NM_022817.3 link	c.231-88A>C		intron_variant	Intron 2 of 22	ENST00000254657.8	NP_073728.1	O15055-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER2	ENST00000254657.8 link	c.231-88A>C		intron_variant	Intron 2 of 22	1	NM_022817.3	ENSP00000254657.3		O15055-1

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16699

AN:

152118

Hom.:

1215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0406

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.0870

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.0561

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.118

GnomAD4 exome

AF:

0.127

AC:

92511

AN:

729784

Hom.:

6361

AF XY:

0.122

AC XY:

47844

AN XY:

390758

show subpopulations

African (AFR)

AF:

0.0393

AC:

765

AN:

19464

American (AMR)

AF:

0.193

AC:

8380

AN:

43426

Ashkenazi Jewish (ASJ)

AF:

0.0939

AC:

2019

AN:

21512

East Asian (EAS)

AF:

0.111

AC:

4044

AN:

36442

South Asian (SAS)

AF:

0.0528

AC:

3752

AN:

71092

European-Finnish (FIN)

AF:

0.160

AC:

8282

AN:

51914

Middle Eastern (MID)

AF:

0.0635

AC:

267

AN:

4202

European-Non Finnish (NFE)

AF:

0.136

AC:

60650

AN:

445412

Other (OTH)

AF:

0.120

AC:

4352

AN:

36320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

4202

8404

12606

16808

21010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

968

1936

2904

3872

4840

<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:

0.110

AC:

16705

AN:

152236

Hom.:

1215

Cov.:

AF XY:

0.110

AC XY:

8225

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0405

AC:

1681

AN:

41556

American (AMR)

AF:

0.172

AC:

2622

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0870

AC:

302

AN:

3470

East Asian (EAS)

AF:

0.106

AC:

550

AN:

5188

South Asian (SAS)

AF:

0.0564

AC:

272

AN:

4826

European-Finnish (FIN)

AF:

0.154

AC:

1629

AN:

10604

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9264

AN:

67990

Other (OTH)

AF:

0.118

AC:

248

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

746

1492

2239

2985

3731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.127

Hom.:

1902

Bravo

AF:

0.109

Asia WGS

AF:

0.0720

AC:

248

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.19

(source)

DANN

Benign

0.65

PhyloP100

-0.41

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over