2-238295120-T-C

Variant names:

• chr2-238295120-T-C
• rs4663302
• XM_047446231.1:c.-159+3520A>G

Variant summary

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

The XR_002959458.2(LOC112268433):​n.30-3257T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,182 control chromosomes in the GnomAD database, including 41,249 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 0.73 (41249 hom., cov: 32)
• Consequence: LOC112268433 XR_002959458.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 16 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)

ENSG00000283635 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000637634.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283635	ENST00000637634.1	TSL:5	n.672-613T>C		intron	N/A
	ENSG00000232306	ENST00000790915.1		n.*101A>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110511 AN: 152064 Hom.: 41192 Cov.: 32

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.727 AC: 110624 AN: 152182 Hom.: 41249 Cov.: 32 AF XY: 0.729 AC XY: 54265 AN XY: 74404

African (AFR) AF: 0.898 AC: 37326 AN: 41544

American (AMR) AF: 0.624 AC: 9538 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2253 AN: 3466

East Asian (EAS) AF: 0.668 AC: 3455 AN: 5176

South Asian (SAS) AF: 0.708 AC: 3420 AN: 4828

European-Finnish (FIN) AF: 0.746 AC: 7900 AN: 10596

Middle Eastern (MID) AF: 0.654 AC: 191 AN: 292

European-Non Finnish (NFE) AF: 0.657 AC: 44638 AN: 67972

Other (OTH) AF: 0.680 AC: 1434 AN: 2110

Alfa AF: 0.670 Hom.: 14573

Bravo AF: 0.719

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.91
DANN	Benign	0.47
PhyloP100		-2.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4663302; hg19: chr2-239203761;