rs12579350

chr12-5687935-G-Achr12-5687935-G-T

Variant summary

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

The NM_001364791.2(ANO2):c.1546-40134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,178 control chromosomes in the GnomAD database, including 1,227 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 0.12 (1227 hom., cov: 33)
• Consequence: ANO2 NM_001364791.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.603

Genes affected

ANO2 (HGNC:1183): (anoctamin 2) ANO2 belongs to a family of calcium-activated chloride channels (CaCCs) (reviewed by Hartzell et al., 2009 [PubMed 19015192]).[supplied by OMIM, Jan 2011]

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 = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO2	NM_001364791.2	c.1546-40134C>T		intron_variant		ENST00000682330.1
ANO2	NM_001278596.3	c.1561-40134C>T		intron_variant
ANO2	NM_001278597.3	c.1549-40134C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO2	ENST00000682330.1	c.1546-40134C>T		intron_variant			NM_001364791.2	P4

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18145 AN: 152060 Hom.: 1224 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0863

Gnomad FIN AF: 0.0902

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0855

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.119 AC: 18161 AN: 152178 Hom.: 1227 Cov.: 33 AF XY: 0.118 AC XY: 8748 AN XY: 74402

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.0859

Gnomad4 FIN AF: 0.0902

Gnomad4 NFE AF: 0.0855

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0859 Hom.: 694

Bravo AF: 0.123

Asia WGS AF: 0.117 AC: 406 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	6.3
Dann	Benign	0.70

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: rs12579350; hg19: chr12-5797101;