2-238276865-T-C

Variant names:

• chr2-238276865-T-C
• rs56013859
• NM_022817.3:c.293+266A>G

Variant summary

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

The NM_022817.3(PER2):​c.293+266A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,044 control chromosomes in the GnomAD database, including 1,213 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 0.11 (1213 hom., cov: 32)
• Consequence: PER2 NM_022817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 14 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022817.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER2	NM_022817.3	MANE Select	c.293+266A>G		intron	N/A	NP_073728.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER2	ENST00000254657.8	TSL:1 MANE Select	c.293+266A>G		intron	N/A	ENSP00000254657.3
	PER2	ENST00000355768.6	TSL:1	n.293+266A>G		intron	N/A
	PER2	ENST00000707129.1		c.293+266A>G		intron	N/A	ENSP00000516757.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16690 AN: 151926 Hom.: 1213 Cov.: 32

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.0871

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0556

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.110 AC: 16696 AN: 152044 Hom.: 1213 Cov.: 32 AF XY: 0.111 AC XY: 8214 AN XY: 74312

African (AFR) AF: 0.0405 AC: 1678 AN: 41448

American (AMR) AF: 0.172 AC: 2625 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0871 AC: 302 AN: 3468

East Asian (EAS) AF: 0.105 AC: 541 AN: 5164

South Asian (SAS) AF: 0.0559 AC: 269 AN: 4812

European-Finnish (FIN) AF: 0.154 AC: 1625 AN: 10570

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9270 AN: 67968

Other (OTH) AF: 0.118 AC: 249 AN: 2112

Alfa AF: 0.0636 Hom.: 84

Bravo AF: 0.109

Asia WGS AF: 0.0720 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.34
DANN	Benign	0.77
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs56013859; hg19: chr2-239185506;