12-5598206-T-G

Position:

• chr12-5598206-T-G

Variant summary

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

The NM_001364791.2(ANO2):​c.2233+1278A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,040 control chromosomes in the GnomAD database, including 6,730 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 0.29 (6730 hom., cov: 32)
• Consequence: ANO2 NM_001364791.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO2	NM_001364791.2	c.2233+1278A>C		intron_variant		ENST00000682330.1	NP_001351720.1
ANO2	NM_001278596.3	c.2248+1278A>C		intron_variant			NP_001265525.1
ANO2	NM_001278597.3	c.2236+1278A>C		intron_variant			NP_001265526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO2	ENST00000682330.1	c.2233+1278A>C		intron_variant			NM_001364791.2	ENSP00000507275	P4
ANO2	ENST00000356134.9	c.2236+1278A>C		intron_variant		5		ENSP00000348453
ANO2	ENST00000650848.1	c.2248+1278A>C		intron_variant				ENSP00000498903	A2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44672 AN: 151922 Hom.: 6723 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.294 AC: 44701 AN: 152040 Hom.: 6730 Cov.: 32 AF XY: 0.290 AC XY: 21558 AN XY: 74304

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.302

Alfa AF: 0.298 Hom.: 3683

Bravo AF: 0.295

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.75

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: rs728342; hg19: chr12-5707372;