dbSNP rs2304674: PER2:c.449-72T>C (chr2-238273263-A-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.449-72T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,497,376 control chromosomes in the GnomAD database, including 63,915 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 0.34 ( 9605 hom., cov: 33)

Exomes 𝑓: 0.28 ( 54310 hom. )

Consequence

PER2
NM_022817.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.766

Publications

24 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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER2	NM_022817.3 link	c.449-72T>C		intron_variant	Intron 4 of 22	ENST00000254657.8	NP_073728.1	O15055-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PER2	ENST00000254657.8 link	c.449-72T>C	intron_variant	Intron 4 of 22	1	NM_022817.3	ENSP00000254657.3	O15055-1
PER2	ENST00000355768.6 link	n.449-72T>C	intron_variant	Intron 3 of 9	1
PER2	ENST00000707129.1 link	c.449-72T>C	intron_variant	Intron 4 of 22			ENSP00000516757.1	O15055-1
PER2	ENST00000707130.1 link	c.449-72T>C	intron_variant	Intron 4 of 22			ENSP00000516758.1	O15055-1

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51872

AN:

151936

Hom.:

9594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.480

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.311

GnomAD4 exome

AF:

0.281

AC:

377460

AN:

1345322

Hom.:

54310

AF XY:

0.281

AC XY:

188898

AN XY:

671880

show subpopulations

African (AFR)

AF:

0.488

AC:

15256

AN:

31232

American (AMR)

AF:

0.266

AC:

10635

AN:

40026

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

5932

AN:

25010

East Asian (EAS)

AF:

0.282

AC:

10692

AN:

37930

South Asian (SAS)

AF:

0.306

AC:

24753

AN:

80882

European-Finnish (FIN)

AF:

0.406

AC:

18787

AN:

46222

Middle Eastern (MID)

AF:

0.283

AC:

1575

AN:

5568

European-Non Finnish (NFE)

AF:

0.268

AC:

273681

AN:

1022050

Other (OTH)

AF:

0.286

AC:

16149

AN:

56402

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

12278

24555

36833

49110

61388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9098

18196

27294

36392

45490

<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:

0.341

AC:

51923

AN:

152054

Hom.:

9605

Cov.:

AF XY:

0.347

AC XY:

25772

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.480

AC:

19912

AN:

41446

American (AMR)

AF:

0.287

AC:

4376

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

833

AN:

3468

East Asian (EAS)

AF:

0.268

AC:

1385

AN:

5170

South Asian (SAS)

AF:

0.312

AC:

1504

AN:

4822

European-Finnish (FIN)

AF:

0.421

AC:

4454

AN:

10568

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.272

AC:

18516

AN:

67996

Other (OTH)

AF:

0.308

AC:

649

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1685

3370

5054

6739

8424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<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:

0.296

Hom.:

13174

Bravo

AF:

0.336

Asia WGS

AF:

0.273

AC:

950

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.083

(source)

DANN

Benign

0.29

PhyloP100

-0.77

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

Computational scores

Splicing

Publications

Other links and lift over