dbSNP rs2292910: CRY2:c.*1151A>C (chr11-45882062-A-C) – 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.*1151A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,180 control chromosomes in the GnomAD database, including 32,799 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 0.65 ( 32778 hom., cov: 33)

Exomes 𝑓: 0.78 ( 21 hom. )

Consequence

CRY2
NM_021117.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.144

Publications

37 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=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY2	NM_021117.5 link	c.*1151A>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000616080.2	NP_066940.3	Q49AN0-1A0A0D2X7Z3A2I2P1
CRY2	NM_001127457.3 link	c.*1151A>C		3_prime_UTR_variant	Exon 12 of 12		NP_001120929.1	Q49AN0-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRY2	ENST00000616080.2 link	c.*1151A>C	3_prime_UTR_variant	Exon 12 of 12	1	NM_021117.5	ENSP00000484684.1	Q49AN0-1
CRY2	ENST00000443527.6 link	c.*1151A>C	3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000406751.2	A0A0D2X7Z3
CRY2	ENST00000616623.4 link	c.*1151A>C	3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000478187.1	A0A0D2X7Z3

Frequencies

GnomAD3 genomes

AF:

0.652

AC:

99053

AN:

151998

Hom.:

32743

Cov.:

show subpopulations

Gnomad AFR

AF:

0.648

Gnomad AMI

AF:

0.687

Gnomad AMR

AF:

0.720

Gnomad ASJ

AF:

0.659

Gnomad EAS

AF:

0.307

Gnomad SAS

AF:

0.593

Gnomad FIN

AF:

0.661

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.667

Gnomad OTH

AF:

0.659

GnomAD4 exome

AF:

0.781

AC:

AN:

Hom.:

Cov.:

AF XY:

0.792

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.833

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.761

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.652

AC:

99142

AN:

152116

Hom.:

32778

Cov.:

AF XY:

0.650

AC XY:

48383

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.648

AC:

26873

AN:

41476

American (AMR)

AF:

0.720

AC:

11017

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.659

AC:

2285

AN:

3470

East Asian (EAS)

AF:

0.307

AC:

1585

AN:

5164

South Asian (SAS)

AF:

0.592

AC:

2855

AN:

4820

European-Finnish (FIN)

AF:

0.661

AC:

6998

AN:

10588

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.667

AC:

45322

AN:

67988

Other (OTH)

AF:

0.661

AC:

1395

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1780

3559

5339

7118

8898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<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:

0.667

Hom.:

43859

Bravo

AF:

0.654

Asia WGS

AF:

0.509

AC:

1774

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.6

(source)

DANN

Benign

0.86

PhyloP100

0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over