rs2292910

chr11-45882062-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CRY2	NM_021117.5	c.*1151A>C		3_prime_UTR_variant	12/12	ENST00000616080.2
CRY2	NM_001127457.3	c.*1151A>C		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRY2	ENST00000616080.2	c.*1151A>C		3_prime_UTR_variant	12/12	1	NM_021117.5	P2
CRY2	ENST00000443527.6	c.*1151A>C		3_prime_UTR_variant	12/12	1		A2
CRY2	ENST00000616623.4	c.*1151A>C		3_prime_UTR_variant	12/12	1		A2

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99053 AN: 151998 Hom.: 32743 Cov.: 33

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: 50 AN: 64 Hom.: 21 Cov.: 0 AF XY: 0.792 AC XY: 38 AN XY: 48

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.761

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.652 AC: 99142 AN: 152116 Hom.: 32778 Cov.: 33 AF XY: 0.650 AC XY: 48383 AN XY: 74382

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.720

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.661

Alfa AF: 0.668 Hom.: 33663

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
Dann	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs2292910; hg19: chr11-45903613;