12-27346668-T-C

Variant summary

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

The NM_020183.6(BMAL2):c.31+13565T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,202 control chromosomes in the GnomAD database, including 1,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.13 (1408 hom., cov: 32)
• Consequence: BMAL2 NM_020183.6 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.0690

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL2	NM_020183.6	c.31+13565T>C		intron_variant		ENST00000266503.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL2	ENST00000266503.10	c.31+13565T>C		intron_variant		1	NM_020183.6	P2

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19261 AN: 152084 Hom.: 1406 Cov.: 32

Gnomad AFR AF: 0.0654

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0999

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0622

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.127 AC: 19271 AN: 152202 Hom.: 1408 Cov.: 32 AF XY: 0.125 AC XY: 9323 AN XY: 74414

Gnomad4 AFR AF: 0.0655

Gnomad4 AMR AF: 0.0997

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0622

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.130

Alfa AF: 0.153 Hom.: 1805

Bravo AF: 0.117

Asia WGS AF: 0.117 AC: 409 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to Other:1

association, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 09, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.7
Dann	Benign	0.57

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: rs17497857; hg19: chr12-27499601;