12-27380300-TT-CG

Variant names:

• chr12-27380300-TT-CG
• NM_020183.6:c.380_381delTTinsCG
• BMAL2 p.Ile127Thr

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_020183.6(BMAL2):​c.380_381delTTinsCG​(p.Ile127Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BMAL2 NM_020183.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.99
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020183.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL2	NM_020183.6	MANE Select	c.380_381delTTinsCG	p.Ile127Thr	missense	N/A	NP_064568.3
	BMAL2	NM_001394524.1		c.413_414delTTinsCG	p.Ile138Thr	missense	N/A	NP_001381453.1
	BMAL2	NM_001394525.1		c.371_372delTTinsCG	p.Ile124Thr	missense	N/A	NP_001381454.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL2	ENST00000266503.10	TSL:1 MANE Select	c.380_381delTTinsCG	p.Ile127Thr	missense	N/A	ENSP00000266503.5	Q8WYA1-1
	BMAL2	ENST00000311001.9	TSL:1	c.338_339delTTinsCG	p.Ile113Thr	missense	N/A	ENSP00000312247.5	Q8WYA1-2
	BMAL2	ENST00000395901.6	TSL:1	c.269_270delTTinsCG	p.Ile90Thr	missense	N/A	ENSP00000379238.2	Q8WYA1-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-27533233;