12-5686577-C-T

Variant names:

• chr12-5686577-C-T
• rs3782631
• NM_001364791.2:c.1546-38776G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ANO2	NM_001364791.2	c.1546-38776G>A		intron_variant	Intron 14 of 24	ENST00000682330.1	NP_001351720.1
ANO2	NM_001278596.3	c.1561-38776G>A		intron_variant	Intron 16 of 26		NP_001265525.1
ANO2	NM_001278597.3	c.1549-38776G>A		intron_variant	Intron 16 of 26		NP_001265526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO2	ENST00000682330.1	c.1546-38776G>A		intron_variant	Intron 14 of 24		NM_001364791.2	ENSP00000507275.1

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

African (AFR) AF: 0.144 AC: 5962 AN: 41500

American (AMR) AF: 0.393 AC: 5997 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1260 AN: 3468

East Asian (EAS) AF: 0.590 AC: 3039 AN: 5152

South Asian (SAS) AF: 0.498 AC: 2399 AN: 4822

European-Finnish (FIN) AF: 0.547 AC: 5761 AN: 10524

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31207 AN: 67948

Other (OTH) AF: 0.374 AC: 788 AN: 2108

Alfa AF: 0.429 Hom.: 9093

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
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3782631; hg19: chr12-5795743;