dbSNP rs10462023: PER2:c.294-43C>T (chr2-238275940-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022817.3(PER2):c.294-43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,606,298 control chromosomes in the GnomAD database, including 102,916 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 0.27 ( 6882 hom., cov: 32)

Exomes 𝑓: 0.36 ( 96034 hom. )

Consequence

PER2
NM_022817.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER2	NM_022817.3 link	c.294-43C>T		intron_variant	Intron 3 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.294-43C>T		intron_variant	Intron 3 of 22	1	NM_022817.3	ENSP00000254657.3		O15055-1

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41655

AN:

152110

Hom.:

6884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0876

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.236

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.266

GnomAD3 exomes

AF:

0.315

AC:

78899

AN:

250844

Hom.:

13243

AF XY:

0.321

AC XY:

43526

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.0831

Gnomad AMR exome

AF:

0.261

Gnomad ASJ exome

AF:

0.352

Gnomad EAS exome

AF:

0.236

Gnomad SAS exome

AF:

0.289

Gnomad FIN exome

AF:

0.331

Gnomad NFE exome

AF:

0.376

Gnomad OTH exome

AF:

0.335

GnomAD4 exome

AF:

0.357

AC:

518402

AN:

1454070

Hom.:

96034

Cov.:

AF XY:

0.355

AC XY:

256936

AN XY:

723930

show subpopulations

Gnomad4 AFR exome

AF:

0.0726

Gnomad4 AMR exome

AF:

0.262

Gnomad4 ASJ exome

AF:

0.362

Gnomad4 EAS exome

AF:

0.213

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.336

Gnomad4 NFE exome

AF:

0.382

Gnomad4 OTH exome

AF:

0.335

GnomAD4 genome

AF:

0.274

AC:

41656

AN:

152228

Hom.:

6882

Cov.:

AF XY:

0.273

AC XY:

20283

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0877

Gnomad4 AMR

AF:

0.279

Gnomad4 ASJ

AF:

0.365

Gnomad4 EAS

AF:

0.236

Gnomad4 SAS

AF:

0.292

Gnomad4 FIN

AF:

0.331

Gnomad4 NFE

AF:

0.374

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.352

Hom.:

15156

Bravo

AF:

0.261

Asia WGS

AF:

0.255

AC:

886

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.090

DANN

Benign

0.67

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over