rs70965449

Variant names:

• chr2-238256893-C-A
• rs70965449
• NM_022817.3:c.2065+29G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -8 ACMG points.

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

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.2065+29G>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.2065+29G>T		intron	N/A	ENSP00000254657.3	O15055-1
	PER2	ENST00000707129.1		c.2065+29G>T		intron	N/A	ENSP00000516757.1	O15055-1
	PER2	ENST00000707130.1		c.2065+29G>T		intron	N/A	ENSP00000516758.1	O15055-1

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

GnomAD2 exomes AF: 0.00873 AC: 2156 AN: 246920 AF XY: 0.00894

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 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

African (AFR) AF: 0.00199 AC: 66 AN: 33200

American (AMR) AF: 0.00793 AC: 346 AN: 43612

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 608 AN: 25426

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39628

South Asian (SAS) AF: 0.00331 AC: 283 AN: 85518

European-Finnish (FIN) AF: 0.00291 AC: 155 AN: 53176

Middle Eastern (MID) AF: 0.00821 AC: 47 AN: 5726

European-Non Finnish (NFE) AF: 0.0131 AC: 14451 AN: 1106792

Other (OTH) AF: 0.0101 AC: 609 AN: 60026

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

African (AFR) AF: 0.00238 AC: 99 AN: 41580

American (AMR) AF: 0.00940 AC: 144 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 63 AN: 3420

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4832

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0129 AC: 875 AN: 68022

Other (OTH) AF: 0.0109 AC: 23 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.3
DANN	Benign	0.61
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism

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: rs70965449; hg19: chr2-239165534;