Genetic Variant ENSG00000283635:n.672-613T>C (chr2-238295120-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000637634.1(ENSG00000283635):n.672-613T>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

ENSG00000283635
ENST00000637634.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.17

Publications

16 publications found

Variant links:

Genes affected

ENSG00000283635 (HGNC:):

ENSG00000283635 links:

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)

PER2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
PER2	XM_047446231.1 link	c.-159+3520A>G	intron_variant	Intron 2 of 24	XP_047302187.1
PER2	XM_047446232.1 link	c.-159+4682A>G	intron_variant	Intron 1 of 23	XP_047302188.1
LOC112268433	XR_002959458.2 link	n.30-3257T>C	intron_variant	Intron 1 of 2
LOC112268433	XR_007088147.1 link	n.837-3257T>C	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283635	ENST00000637634.1 link	n.672-613T>C		intron_variant	Intron 1 of 3	5
ENSG00000232306	ENST00000790915.1 link	n.*101A>G		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.727

AC:

110511

AN:

152064

Hom.:

41192

Cov.:

show subpopulations

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.:

AF XY:

0.729

AC XY:

54265

AN XY:

74404

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1502

3004

4506

6008

7510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.670

Hom.:

14573

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

(source)

DANN

Benign

0.47

PhyloP100

-2.2

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over