rs6431590

Positions:

• chr2-238256487-A-G

Variant summary

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

The ENST00000254657.8(PER2):​c.2065+435T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,098 control chromosomes in the GnomAD database, including 15,444 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 0.42 (15444 hom., cov: 33)
• Consequence: PER2 ENST00000254657.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER2	NM_022817.3	c.2065+435T>C		intron_variant		ENST00000254657.8	NP_073728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER2	ENST00000254657.8	c.2065+435T>C		intron_variant		1	NM_022817.3	ENSP00000254657	P1
PER2	ENST00000707129.1	c.2065+435T>C		intron_variant				ENSP00000516757	P1
PER2	ENST00000707130.1	c.2065+435T>C		intron_variant				ENSP00000516758	P1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64506 AN: 151980 Hom.: 15403 Cov.: 33

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.425 AC: 64615 AN: 152098 Hom.: 15444 Cov.: 33 AF XY: 0.429 AC XY: 31869 AN XY: 74352

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.401

Alfa AF: 0.325 Hom.: 13509

Bravo AF: 0.422

Asia WGS AF: 0.372 AC: 1291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.038
DANN	Benign	0.26

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

Other links and lift over

dbSNP: rs6431590; hg19: chr2-239165128;