Variant 11-45867677-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_021117.5(CRY2):c.807C>T(p.Gly269=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,614,258 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 40 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 31 hom. )

Consequence

CRY2
NM_021117.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.897

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 11-45867677-C-T is Benign according to our data. Variant chr11-45867677-C-T is described in ClinVar as [Benign]. Clinvar id is 780966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.897 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1743/152368) while in subpopulation AFR AF= 0.0402 (1671/41580). AF 95% confidence interval is 0.0386. There are 40 homozygotes in gnomad4. There are 838 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1743 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRY2	NM_021117.5 linkuse as main transcript	c.807C>T	p.Gly269=	synonymous_variant	6/12	ENST00000616080.2
CRY2	NM_001127457.3 linkuse as main transcript	c.624C>T	p.Gly208=	synonymous_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRY2	ENST00000616080.2 linkuse as main transcript	c.807C>T	p.Gly269=	synonymous_variant	6/12	1	NM_021117.5	P2	Q49AN0-1

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1744

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0403

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00313

AC:

786

AN:

251474

Hom.:

AF XY:

0.00238

AC XY:

324

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0423

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.00114

AC:

1660

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000993

AC XY:

722

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0401

Gnomad4 AMR exome

AF:

0.00241

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.00278

GnomAD4 genome

AF:

0.0114

AC:

1743

AN:

152368

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

838

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.0402

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00493

Hom.:

Bravo

AF:

0.0127

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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