rs2289709

Positions:

• chr12-27420700-C-T

Variant summary

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

The NM_020183.6(BMAL2):​c.*168C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 777,024 control chromosomes in the GnomAD database, including 6,726 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 0.13 (1493 hom., cov: 32)
  • Exomes 𝑓: 0.13 (5233 hom.)
• Consequence: BMAL2 NM_020183.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

Genes affected

BMAL2 (HGNC:18984): (basic helix-loop-helix ARNT like 2) This gene encodes a basic helix-loop-helix transcription factor belonging to the PAS (PER, ARNT, SIM) superfamily. The PAS proteins play important roles in adaptation to low atmospheric and cellular oxygen levels, exposure to certain environmental pollutants, and diurnal oscillations in light and temperature. This protein forms a transcriptionally active heterodimer with the circadian CLOCK protein, the structurally related MOP4, and hypoxia-inducible factors, such as HIF1alpha. Consistent with its role as a biologically relevant partner of circadian and hypoxia factors, this protein is coexpressed in regions of the brain such as the thalamus, hypothalamus, and amygdala. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

BMAL2-AS1 (HGNC:49892): (BMAL2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL2	NM_020183.6	c.*168C>T		3_prime_UTR_variant	17/17	ENST00000266503.10
BMAL2-AS1	NR_109975.1	n.138+25797G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL2	ENST00000266503.10	c.*168C>T		3_prime_UTR_variant	17/17	1	NM_020183.6	P2
BMAL2	ENST00000457040.6	c.*168C>T		3_prime_UTR_variant	15/15	1
BMAL2-AS1	ENST00000500498.2	n.129+25797G>A		intron_variant, non_coding_transcript_variant		1
BMAL2	ENST00000544915.5	c.*168C>T		3_prime_UTR_variant	16/16	5		A2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20395 AN: 152062 Hom.: 1472 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0885

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.127 AC: 79180 AN: 624844 Hom.: 5233 Cov.: 9 AF XY: 0.127 AC XY: 39410 AN XY: 309152

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.0676

Gnomad4 ASJ exome AF: 0.0763

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.134 AC: 20452 AN: 152180 Hom.: 1493 Cov.: 32 AF XY: 0.133 AC XY: 9895 AN XY: 74400

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0884

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.116

Alfa AF: 0.116 Hom.: 1422

Bravo AF: 0.132

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.74

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: rs2289709; hg19: chr12-27573633; COSMIC: COSV99668248; COSMIC: COSV99668248;