Variant 2-238246532-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022817.3(PER2):c.3619-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000318 in 1,352,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PER2
NM_022817.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004755

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.697

Variant links:

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 2-238246532-G-A is Benign according to our data. Variant chr2-238246532-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1090358.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PER2	NM_022817.3 linkuse as main transcript	c.3619-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000254657.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
PER2	ENST00000254657.8 linkuse as main transcript	c.3619-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_022817.3	P1	O15055-1
	ENST00000456601.1 linkuse as main transcript	n.1231+54G>A	intron_variant, non_coding_transcript_variant	2
PER2	ENST00000707129.1 linkuse as main transcript	c.3619-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			P1
PER2	ENST00000707130.1 linkuse as main transcript	c.3619-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150380

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000113

AC:

AN:

212984

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

116222

show subpopulations

Gnomad AFR exome

AF:

0.000143

Gnomad AMR exome

AF:

0.000142

Gnomad ASJ exome

AF:

0.000114

Gnomad EAS exome

AF:

0.000454

Gnomad SAS exome

AF:

0.0000376

Gnomad FIN exome

AF:

0.000110

Gnomad NFE exome

AF:

0.0000621

Gnomad OTH exome

AF:

0.000193

GnomAD4 exome

AF:

0.0000318

AC:

AN:

1352750

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

677972

show subpopulations

Gnomad4 AFR exome

AF:

0.000131

Gnomad4 AMR exome

AF:

0.000468

Gnomad4 ASJ exome

AF:

0.000121

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000137

Gnomad4 OTH exome

AF:

0.0000533

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000665

AC:

AN:

150380

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73336

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000425

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

Cadd

Benign

9.4

Dann

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000048

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over