dbSNP rs10838527: CRY2:c.*732A>G (chr11-45881643-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_021117.5(CRY2):c.*732A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,214 control chromosomes in the GnomAD database, including 1,504 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 0.12 ( 1504 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CRY2
NM_021117.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.512

Publications

24 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY2	NM_021117.5 link	c.*732A>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000616080.2	NP_066940.3
CRY2	NM_001127457.3 link	c.*732A>G		3_prime_UTR_variant	Exon 12 of 12		NP_001120929.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CRY2	ENST00000616080.2 link	c.*732A>G	3_prime_UTR_variant	Exon 12 of 12	1	NM_021117.5	ENSP00000484684.1
CRY2	ENST00000443527.6 link	c.*732A>G	3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000406751.2
CRY2	ENST00000616623.4 link	c.*732A>G	3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000478187.1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18158

AN:

152096

Hom.:

1500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0808

Gnomad ASJ

AF:

0.0320

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0182

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0820

Gnomad OTH

AF:

0.105

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.119

AC:

18174

AN:

152214

Hom.:

1504

Cov.:

AF XY:

0.119

AC XY:

8839

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.233

AC:

9677

AN:

41500

American (AMR)

AF:

0.0806

AC:

1234

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0320

AC:

111

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.0180

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.118

AC:

1248

AN:

10594

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0820

AC:

5574

AN:

68014

Other (OTH)

AF:

0.104

AC:

219

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

769

1538

2307

3076

3845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

186

372

558

744

930

<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:

0.0880

Hom.:

1400

Bravo

AF:

0.120

Asia WGS

AF:

0.0290

AC:

101

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.4

(source)

DANN

Benign

0.83

PhyloP100

-0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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