rs70965449

Positions:

• chr2-238256893-C-A
• chr2-238256893-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_022817.3(PER2):​c.2065+29G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,605,394 control chromosomes in the GnomAD database, including 123 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 0.0082 (7 hom., cov: 33)
  • Exomes 𝑓: 0.011 (116 hom.)
• Consequence: PER2 NM_022817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS2: High AC in GnomAd4 at 1251 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER2	NM_022817.3	c.2065+29G>T		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+29G>T		intron_variant		1	NM_022817.3	ENSP00000254657	P1
PER2	ENST00000707129.1	c.2065+29G>T		intron_variant				ENSP00000516757	P1
PER2	ENST00000707130.1	c.2065+29G>T		intron_variant				ENSP00000516758	P1

Frequencies

GnomAD3 genomes AF: 0.00823 AC: 1252 AN: 152172 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00948

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00873 AC: 2156 AN: 246920 Hom.: 10 AF XY: 0.00894 AC XY: 1194 AN XY: 133600

Gnomad AFR exome AF: 0.00230

Gnomad AMR exome AF: 0.00736

Gnomad ASJ exome AF: 0.0242

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.00261

Gnomad FIN exome AF: 0.00266

Gnomad NFE exome AF: 0.0127

Gnomad OTH exome AF: 0.0116

GnomAD4 exome AF: 0.0114 AC: 16566 AN: 1453104 Hom.: 116 Cov.: 29 AF XY: 0.0114 AC XY: 8225 AN XY: 722888

Gnomad4 AFR exome AF: 0.00199

Gnomad4 AMR exome AF: 0.00793

Gnomad4 ASJ exome AF: 0.0239

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00331

Gnomad4 FIN exome AF: 0.00291

Gnomad4 NFE exome AF: 0.0131

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.00821 AC: 1251 AN: 152290 Hom.: 7 Cov.: 33 AF XY: 0.00789 AC XY: 588 AN XY: 74480

Gnomad4 AFR AF: 0.00238

Gnomad4 AMR AF: 0.00940

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00926 Hom.: 1

Bravo AF: 0.00874

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.3
DANN	Benign	0.61

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: rs70965449; hg19: chr2-239165534;