dbSNP rs70965449: PER2:c.2065+29G>T (chr2-238256893-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_022817.3(PER2):c.2065+29G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,605,394 control chromosomes in the GnomAD database, including 123 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 0.0082 ( 7 hom., cov: 33)

Exomes 𝑓: 0.011 ( 116 hom. )

Consequence

PER2
NM_022817.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.184

Publications

1 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BS2

High AC in GnomAd4 at 1251 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER2	NM_022817.3 link	c.2065+29G>T		intron_variant	Intron 17 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.2065+29G>T	intron_variant	Intron 17 of 22	1	NM_022817.3	ENSP00000254657.3	O15055-1
PER2	ENST00000707129.1 link	c.2065+29G>T	intron_variant	Intron 17 of 22			ENSP00000516757.1	O15055-1
PER2	ENST00000707130.1 link	c.2065+29G>T	intron_variant	Intron 17 of 22			ENSP00000516758.1	O15055-1

Frequencies

GnomAD3 genomes

AF:

0.00823

AC:

1252

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00948

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00873

AC:

2156

AN:

246920

AF XY:

0.00894

show subpopulations

Gnomad AFR exome

AF:

0.00230

Gnomad AMR exome

AF:

0.00736

Gnomad ASJ exome

AF:

0.0242

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00266

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.0114

AC:

16566

AN:

1453104

Hom.:

116

Cov.:

AF XY:

0.0114

AC XY:

8225

AN XY:

722888

show subpopulations

African (AFR)

AF:

0.00199

AC:

AN:

33200

American (AMR)

AF:

0.00793

AC:

346

AN:

43612

Ashkenazi Jewish (ASJ)

AF:

0.0239

AC:

608

AN:

25426

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39628

South Asian (SAS)

AF:

0.00331

AC:

283

AN:

85518

European-Finnish (FIN)

AF:

0.00291

AC:

155

AN:

53176

Middle Eastern (MID)

AF:

0.00821

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0131

AC:

14451

AN:

1106792

Other (OTH)

AF:

0.0101

AC:

609

AN:

60026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

688

1375

2063

2750

3438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

532

1064

1596

2128

2660

<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:

0.00821

AC:

1251

AN:

152290

Hom.:

Cov.:

AF XY:

0.00789

AC XY:

588

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00238

AC:

AN:

41580

American (AMR)

AF:

0.00940

AC:

144

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

3420

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00352

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0129

AC:

875

AN:

68022

Other (OTH)

AF:

0.0109

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

134

202

269

336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00926

Hom.:

Bravo

AF:

0.00874

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.3

(source)

DANN

Benign

0.61

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism

(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