dbSNP rs1401419: CRY2:c.325-543T>C (chr11-45858188-T-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.325-543T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,240 control chromosomes in the GnomAD database, including 14,568 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 0.40 ( 14550 hom., cov: 32)

Exomes 𝑓: 0.52 ( 18 hom. )

Consequence

CRY2
NM_021117.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0340

Publications

12 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY2	NM_021117.5 link	c.325-543T>C		intron_variant	Intron 2 of 11	ENST00000616080.2	NP_066940.3	Q49AN0-1A0A0D2X7Z3A2I2P1
CRY2	NM_001127457.3 link	c.142-543T>C		intron_variant	Intron 2 of 11		NP_001120929.1	Q49AN0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRY2	ENST00000616080.2 link	c.325-543T>C		intron_variant	Intron 2 of 11	1	NM_021117.5	ENSP00000484684.1		Q49AN0-1

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60400

AN:

151998

Hom.:

14541

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.574

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.504

Gnomad FIN

AF:

0.478

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.433

GnomAD4 exome

AF:

0.524

AC:

AN:

124

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.583

AC:

AN:

108

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.397

AC:

60422

AN:

152116

Hom.:

14550

Cov.:

AF XY:

0.399

AC XY:

29662

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.124

AC:

5130

AN:

41516

American (AMR)

AF:

0.501

AC:

7647

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.574

AC:

1994

AN:

3472

East Asian (EAS)

AF:

0.242

AC:

1255

AN:

5176

South Asian (SAS)

AF:

0.504

AC:

2430

AN:

4822

European-Finnish (FIN)

AF:

0.478

AC:

5047

AN:

10568

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.520

AC:

35357

AN:

67972

Other (OTH)

AF:

0.437

AC:

924

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1670

3341

5011

6682

8352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.438

Hom.:

2118

Bravo

AF:

0.386

Asia WGS

AF:

0.393

AC:

1371

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.1

(source)

DANN

Benign

0.65

PhyloP100

-0.034

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