12-5625021-A-G

Variant names:

• chr12-5625021-A-G
• rs2110169
• NM_001364791.2:c.1817-9724T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364791.2(ANO2):​c.1817-9724T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,056 control chromosomes in the GnomAD database, including 7,368 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 (7368 hom., cov: 32)
• Consequence: ANO2 NM_001364791.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561
• Publications: 0 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364791.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO2	NM_001364791.2	MANE Select	c.1817-9724T>C		intron	N/A	NP_001351720.1
	ANO2	NM_001278596.3		c.1832-9724T>C		intron	N/A	NP_001265525.1
	ANO2	NM_001278597.3		c.1820-9724T>C		intron	N/A	NP_001265526.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO2	ENST00000682330.1	MANE Select	c.1817-9724T>C		intron	N/A	ENSP00000507275.1
	ANO2	ENST00000650848.1		c.1832-9724T>C		intron	N/A	ENSP00000498903.1
	ANO2	ENST00000356134.9	TSL:5	c.1820-9724T>C		intron	N/A	ENSP00000348453.5

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43363 AN: 151938 Hom.: 7374 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.285 AC: 43354 AN: 152056 Hom.: 7368 Cov.: 32 AF XY: 0.285 AC XY: 21194 AN XY: 74312

African (AFR) AF: 0.102 AC: 4236 AN: 41534

American (AMR) AF: 0.248 AC: 3788 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1212 AN: 3468

East Asian (EAS) AF: 0.484 AC: 2480 AN: 5126

South Asian (SAS) AF: 0.407 AC: 1958 AN: 4808

European-Finnish (FIN) AF: 0.298 AC: 3155 AN: 10572

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25431 AN: 67968

Other (OTH) AF: 0.290 AC: 612 AN: 2108

Alfa AF: 0.300 Hom.: 1271

Bravo AF: 0.271

Asia WGS AF: 0.402 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.68
DANN	Benign	0.63
PhyloP100		-0.56
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: rs2110169; hg19: chr12-5734187;