chr12-5872187-C-T

Position:

• chr12-5872187-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.535-18046G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 152,084 control chromosomes in the GnomAD database, including 877 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 0.071 (877 hom., cov: 32)
• Consequence: ANO2 NM_001364791.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO2	NM_001364791.2	c.535-18046G>A		intron_variant		ENST00000682330.1	NP_001351720.1
ANO2	NM_001278596.3	c.535-18046G>A		intron_variant			NP_001265525.1
ANO2	NM_001278597.3	c.523-18046G>A		intron_variant			NP_001265526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO2	ENST00000682330.1	c.535-18046G>A		intron_variant			NM_001364791.2	ENSP00000507275	P4
ANO2	ENST00000356134.9	c.523-18046G>A		intron_variant		5		ENSP00000348453
ANO2	ENST00000650848.1	c.535-18046G>A		intron_variant				ENSP00000498903	A2
ANO2	ENST00000541487.1	n.28+9592G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0706 AC: 10727 AN: 151966 Hom.: 874 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0401

Gnomad ASJ AF: 0.0624

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.00462

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0593

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

GnomAD4 genome AF: 0.0708 AC: 10763 AN: 152084 Hom.: 877 Cov.: 32 AF XY: 0.0675 AC XY: 5022 AN XY: 74346

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.0401

Gnomad4 ASJ AF: 0.0624

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0162

Gnomad4 FIN AF: 0.00462

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.0587

Alfa AF: 0.0333 Hom.: 84

Bravo AF: 0.0793

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.91
DANN	Benign	0.54

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: rs7307889; hg19: chr12-5981353;