Variant 11-45847462-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000443527.6(CRY2):c.35C>A(p.Ala12Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,596,242 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 47 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 96 hom. )

Consequence

CRY2
ENST00000443527.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.62

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022559166).

BP6

Variant 11-45847462-C-A is Benign according to our data. Variant chr11-45847462-C-A is described in ClinVar as [Benign]. Clinvar id is 782294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRY2	NM_001127457.3 linkuse as main transcript	c.32+181C>A		intron_variant
CRY2	NM_021117.5 linkuse as main transcript			upstream_gene_variant		ENST00000616080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRY2	ENST00000616080.2 linkuse as main transcript			upstream_gene_variant		1	NM_021117.5	P2	Q49AN0-1

Frequencies

GnomAD3 genomes

AF:

0.00710

AC:

1081

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0558

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0233

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.0106

AC:

2387

AN:

225630

Hom.:

AF XY:

0.00850

AC XY:

1058

AN XY:

124540

show subpopulations

Gnomad AFR exome

AF:

0.00131

Gnomad AMR exome

AF:

0.0548

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0243

Gnomad SAS exome

AF:

0.00229

Gnomad FIN exome

AF:

0.0000676

Gnomad NFE exome

AF:

0.000137

Gnomad OTH exome

AF:

0.00902

GnomAD4 exome

AF:

0.00277

AC:

4000

AN:

1443916

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

1826

AN XY:

717016

show subpopulations

Gnomad4 AFR exome

AF:

0.000963

Gnomad4 AMR exome

AF:

0.0533

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0287

Gnomad4 SAS exome

AF:

0.00228

Gnomad4 FIN exome

AF:

0.0000432

Gnomad4 NFE exome

AF:

0.0000887

Gnomad4 OTH exome

AF:

0.00355

GnomAD4 genome

AF:

0.00714

AC:

1088

AN:

152326

Hom.:

Cov.:

AF XY:

0.00904

AC XY:

673

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.0562

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0234

Gnomad4 SAS

AF:

0.00415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00185

Hom.:

Bravo

AF:

0.00948

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00122

AC:

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.00738

AC:

886

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.91

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.33

.;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.14

N;.

REVEL

Benign

0.034

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Vest4

0.34

MPC

0.67

ClinPred

0.13

GERP RS

2.9

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

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