chr2-238295120-T-C

Position:

• chr2-238295120-T-C

Variant summary

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

The XM_047446231.1(PER2):​c.-159+3520A>G 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: PER2 XM_047446231.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

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]

ENSG00000283635 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER2	XM_047446231.1	c.-159+3520A>G		intron_variant			XP_047302187.1
PER2	XM_047446232.1	c.-159+4682A>G		intron_variant			XP_047302188.1
LOC112268433	XR_002959458.2	n.30-3257T>C		intron_variant
LOC112268433	XR_007088147.1	n.837-3257T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000283635	ENST00000637634.1	n.672-613T>C		intron_variant		5

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

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.680

Alfa AF: 0.661 Hom.: 10651

Bravo AF: 0.719

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4663302; hg19: chr2-239203761;