12-5686577-C-T

Variant summary

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

The NM_001364791.2(ANO2):c.1546-38776G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,004 control chromosomes in the GnomAD database, including 12,381 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 0.37 (12381 hom., cov: 32)
• Consequence: ANO2 NM_001364791.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO2	NM_001364791.2	c.1546-38776G>A		intron_variant		ENST00000682330.1
ANO2	NM_001278596.3	c.1561-38776G>A		intron_variant
ANO2	NM_001278597.3	c.1549-38776G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO2	ENST00000682330.1	c.1546-38776G>A		intron_variant			NM_001364791.2	P4

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56826 AN: 151886 Hom.: 12377 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.374 AC: 56833 AN: 152004 Hom.: 12381 Cov.: 32 AF XY: 0.380 AC XY: 28260 AN XY: 74272

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.374

Alfa AF: 0.439 Hom.: 7942

Bravo AF: 0.353

Asia WGS AF: 0.478 AC: 1661 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.6
Dann	Benign	0.33

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: rs3782631; hg19: chr12-5795743;