chr2-238252450-C-T

Variant names:

• chr2-238252450-C-T
• rs4663868
• NM_022817.3:c.3111+462G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022817.3(PER2):​c.3111+462G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 152,268 control chromosomes in the GnomAD database, including 696 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 0.092 (696 hom., cov: 33)
• Consequence: PER2 NM_022817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.626
• Publications: 12 publications found

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)

ENSG00000225057 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER2	NM_022817.3	c.3111+462G>A		intron_variant	Intron 19 of 22	ENST00000254657.8	NP_073728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER2	ENST00000254657.8	c.3111+462G>A		intron_variant	Intron 19 of 22	1	NM_022817.3	ENSP00000254657.3
PER2	ENST00000707129.1	c.3111+462G>A		intron_variant	Intron 19 of 22			ENSP00000516757.1
PER2	ENST00000707130.1	c.3111+462G>A		intron_variant	Intron 19 of 22			ENSP00000516758.1
ENSG00000225057	ENST00000456601.1	n.1525-1738C>T		intron_variant	Intron 5 of 6	2

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13973 AN: 152150 Hom.: 696 Cov.: 33

Gnomad AFR AF: 0.0973

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0483

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0575

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.0833

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0918 AC: 13977 AN: 152268 Hom.: 696 Cov.: 33 AF XY: 0.0961 AC XY: 7156 AN XY: 74438

African (AFR) AF: 0.0971 AC: 4036 AN: 41558

American (AMR) AF: 0.0483 AC: 740 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3472

East Asian (EAS) AF: 0.0574 AC: 298 AN: 5192

South Asian (SAS) AF: 0.127 AC: 614 AN: 4830

European-Finnish (FIN) AF: 0.170 AC: 1802 AN: 10580

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0848 AC: 5767 AN: 68012

Other (OTH) AF: 0.0819 AC: 173 AN: 2112

Alfa AF: 0.0919 Hom.: 354

Bravo AF: 0.0817

Asia WGS AF: 0.0760 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.72
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4663868; hg19: chr2-239161091;