12-5604398-G-A

Position:

• chr12-5604398-G-A

Variant summary

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

The NM_001364791.2(ANO2):​c.2088-4769C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,068 control chromosomes in the GnomAD database, including 16,393 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 0.46 (16393 hom., cov: 32)
• Consequence: ANO2 NM_001364791.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO2	NM_001364791.2	c.2088-4769C>T		intron_variant		ENST00000682330.1
ANO2	NM_001278596.3	c.2103-4769C>T		intron_variant
ANO2	NM_001278597.3	c.2091-4769C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO2	ENST00000682330.1	c.2088-4769C>T		intron_variant			NM_001364791.2	P4
ANO2	ENST00000356134.9	c.2091-4769C>T		intron_variant		5
ANO2	ENST00000650848.1	c.2103-4769C>T		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70347 AN: 151950 Hom.: 16367 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.463 AC: 70409 AN: 152068 Hom.: 16393 Cov.: 32 AF XY: 0.469 AC XY: 34841 AN XY: 74324

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.469

Alfa AF: 0.445 Hom.: 19889

Bravo AF: 0.458

Asia WGS AF: 0.549 AC: 1911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.58

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: rs1558776; hg19: chr12-5713564;