12-5642176-C-T

Position:

• chr12-5642176-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.1620+5551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0585 in 152,228 control chromosomes in the GnomAD database, including 371 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 0.059 (371 hom., cov: 32)
• Consequence: ANO2 NM_001364791.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO2	NM_001364791.2	c.1620+5551G>A		intron_variant		ENST00000682330.1
ANO2	NM_001278596.3	c.1635+5551G>A		intron_variant
ANO2	NM_001278597.3	c.1623+5551G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO2	ENST00000682330.1	c.1620+5551G>A		intron_variant			NM_001364791.2	P4

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 8888 AN: 152110 Hom.: 371 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0562

Gnomad FIN AF: 0.0382

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0303

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0585 AC: 8909 AN: 152228 Hom.: 371 Cov.: 32 AF XY: 0.0616 AC XY: 4582 AN XY: 74430

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0697

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0563

Gnomad4 FIN AF: 0.0382

Gnomad4 NFE AF: 0.0303

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0379 Hom.: 133

Bravo AF: 0.0635

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
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: rs2110166; hg19: chr12-5751342;