rs2304672

Positions:

• chr2-238277948-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022817.3(PER2):​c.-12C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 1,611,976 control chromosomes in the GnomAD database, including 6,907 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 0.093 (710 hom., cov: 33)
  • Exomes 𝑓: 0.086 (6197 hom.)
• Consequence: PER2 NM_022817.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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/exons	MANE	UniProt
PER2	NM_022817.3	c.-12C>G		5_prime_UTR_variant	2/23	ENST00000254657.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PER2	ENST00000254657.8	c.-12C>G		5_prime_UTR_variant	2/23	1	NM_022817.3	P1

Frequencies

GnomAD3 genomes AF: 0.0926 AC: 14092 AN: 152172 Hom.: 709 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0477

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0575

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.0846

GnomAD3 exomes AF: 0.0938 AC: 22785 AN: 242956 Hom.: 1294 AF XY: 0.0982 AC XY: 12939 AN XY: 131782

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.0329

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.0545

Gnomad SAS exome AF: 0.140

Gnomad FIN exome AF: 0.168

Gnomad NFE exome AF: 0.0893

Gnomad OTH exome AF: 0.0927

GnomAD4 exome AF: 0.0864 AC: 126151 AN: 1459686 Hom.: 6197 Cov.: 33 AF XY: 0.0892 AC XY: 64729 AN XY: 726008

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.0345

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.0591

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.163

Gnomad4 NFE exome AF: 0.0802

Gnomad4 OTH exome AF: 0.0917

GnomAD4 genome AF: 0.0926 AC: 14096 AN: 152290 Hom.: 710 Cov.: 33 AF XY: 0.0969 AC XY: 7215 AN XY: 74460

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.0477

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0575

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.0852

Gnomad4 OTH AF: 0.0833

Alfa AF: 0.0970 Hom.: 150

Bravo AF: 0.0826

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.2
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs2304672; hg19: chr2-239186589;