rs10462023

Variant names:

• chr2-238275940-G-A
• rs10462023
• NM_022817.3:c.294-43C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-238275940-G-A
• chr2-238275940-G-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 39 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER2	NM_022817.3	MANE Select	c.294-43C>T		intron	N/A	NP_073728.1	O15055-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER2	ENST00000254657.8	TSL:1 MANE Select	c.294-43C>T		intron	N/A	ENSP00000254657.3	O15055-1
	PER2	ENST00000355768.6	TSL:1	n.294-43C>T		intron	N/A
	PER2	ENST00000707129.1		c.294-43C>T		intron	N/A	ENSP00000516757.1	O15055-1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41655 AN: 152110 Hom.: 6884 Cov.: 32

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

GnomAD2 exomes AF: 0.315 AC: 78899 AN: 250844 AF XY: 0.321

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 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.: 31 AF XY: 0.355 AC XY: 256936 AN XY: 723930

African (AFR) AF: 0.0726 AC: 2411 AN: 33206

American (AMR) AF: 0.262 AC: 11707 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 9436 AN: 26084

East Asian (EAS) AF: 0.213 AC: 8444 AN: 39660

South Asian (SAS) AF: 0.290 AC: 24978 AN: 86078

European-Finnish (FIN) AF: 0.336 AC: 17905 AN: 53304

Middle Eastern (MID) AF: 0.220 AC: 1264 AN: 5754

European-Non Finnish (NFE) AF: 0.382 AC: 422145 AN: 1105212

Other (OTH) AF: 0.335 AC: 20112 AN: 60098

GnomAD4 genome AF: 0.274 AC: 41656 AN: 152228 Hom.: 6882 Cov.: 32 AF XY: 0.273 AC XY: 20283 AN XY: 74420

African (AFR) AF: 0.0877 AC: 3643 AN: 41560

American (AMR) AF: 0.279 AC: 4264 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1268 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1223 AN: 5176

South Asian (SAS) AF: 0.292 AC: 1409 AN: 4832

European-Finnish (FIN) AF: 0.331 AC: 3501 AN: 10578

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25432 AN: 67992

Other (OTH) AF: 0.264 AC: 559 AN: 2116

Alfa AF: 0.331 Hom.: 22588

Bravo AF: 0.261

Asia WGS AF: 0.255 AC: 886 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.090
DANN	Benign	0.67
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10462023; hg19: chr2-239184581; COSMIC: COSV54524025;