Variant rs2292913 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021117.5(CRY2):c.216-4A>G 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 0.915 in 1,612,230 control chromosomes in the GnomAD database, including 681,846 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.89 ( 60920 hom., cov: 32)

Exomes 𝑓: 0.92 ( 620926 hom. )

Consequence

CRY2
NM_021117.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001303

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.602

Variant links:

Genes affected

CRY2 (HGNC:2385): (cryptochrome circadian regulator 2) This gene encodes a flavin adenine dinucleotide-binding protein that is a key component of the circadian core oscillator complex, which regulates the circadian clock. 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 have been associated with altered sleep patterns. The encoded protein is widely conserved across plants and animals. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2014]

CRY2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRY2	NM_021117.5 linkuse as main transcript	c.216-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000616080.2
CRY2	NM_001127457.3 linkuse as main transcript	c.33-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRY2	ENST00000616080.2 linkuse as main transcript	c.216-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_021117.5	P2	Q49AN0-1

Frequencies

GnomAD3 genomes

AF:

0.889

AC:

135303

AN:

152124

Hom.:

60877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.841

Gnomad AMI

AF:

0.979

Gnomad AMR

AF:

0.894

Gnomad ASJ

AF:

0.936

Gnomad EAS

AF:

0.459

Gnomad SAS

AF:

0.861

Gnomad FIN

AF:

0.950

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.940

Gnomad OTH

AF:

0.884

GnomAD3 exomes

AF:

0.879

AC:

220974

AN:

251412

Hom.:

98988

AF XY:

0.882

AC XY:

119905

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.841

Gnomad AMR exome

AF:

0.871

Gnomad ASJ exome

AF:

0.936

Gnomad EAS exome

AF:

0.463

Gnomad SAS exome

AF:

0.874

Gnomad FIN exome

AF:

0.948

Gnomad NFE exome

AF:

0.936

Gnomad OTH exome

AF:

0.901

GnomAD4 exome

AF:

0.918

AC:

1340403

AN:

1459988

Hom.:

620926

Cov.:

AF XY:

0.917

AC XY:

666065

AN XY:

726420

show subpopulations

Gnomad4 AFR exome

AF:

0.840

Gnomad4 AMR exome

AF:

0.874

Gnomad4 ASJ exome

AF:

0.937

Gnomad4 EAS exome

AF:

0.430

Gnomad4 SAS exome

AF:

0.874

Gnomad4 FIN exome

AF:

0.946

Gnomad4 NFE exome

AF:

0.942

Gnomad4 OTH exome

AF:

0.906

GnomAD4 genome

AF:

0.889

AC:

135403

AN:

152242

Hom.:

60920

Cov.:

AF XY:

0.887

AC XY:

66010

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.841

Gnomad4 AMR

AF:

0.894

Gnomad4 ASJ

AF:

0.936

Gnomad4 EAS

AF:

0.458

Gnomad4 SAS

AF:

0.860

Gnomad4 FIN

AF:

0.950

Gnomad4 NFE

AF:

0.940

Gnomad4 OTH

AF:

0.884

Alfa

AF:

0.924

Hom.:

123213

Bravo

AF:

0.880

Asia WGS

AF:

0.760

AC:

2646

AN:

3478

EpiCase

AF:

0.939

EpiControl

AF:

0.935

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.012

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over