ENST00000506722.5:c.21+115473T>G

Variant names:

• chr4-113019987-T-G
• rs2135351
• ENST00000506722.5:c.21+115473T>G

Variant summary

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

The ENST00000506722.5(ANK2):​c.21+115473T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,984 control chromosomes in the GnomAD database, including 26,476 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 0.57 (26476 hom., cov: 31)
• Consequence: ANK2 ENST00000506722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 1 publications found

Genes affected

ANK2 (HGNC:493): (ankyrin 2) This gene encodes a member of the ankyrin family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton. Ankyrins play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. The protein encoded by this gene is required for targeting and stability of Na/Ca exchanger 1 in cardiomyocytes. Mutations in this gene cause long QT syndrome 4 and cardiac arrhythmia syndrome. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2011]

ANK2-AS1 (HGNC:40076): (ANK2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000506722.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK2	NM_001386142.1		c.21+115473T>G		intron	N/A	NP_001373071.1
	ANK2	NM_001386143.1		c.21+115473T>G		intron	N/A	NP_001373072.1
	ANK2	NM_001386186.2		c.73-154429T>G		intron	N/A	NP_001373115.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK2	ENST00000506722.5	TSL:1	c.21+115473T>G		intron	N/A	ENSP00000421067.1
	ANK2	ENST00000672209.1		c.21+115473T>G		intron	N/A	ENSP00000499982.1
	ANK2	ENST00000673298.1		c.21+115473T>G		intron	N/A	ENSP00000500245.1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87153 AN: 151866 Hom.: 26488 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.573 AC: 87143 AN: 151984 Hom.: 26476 Cov.: 31 AF XY: 0.569 AC XY: 42268 AN XY: 74300

African (AFR) AF: 0.360 AC: 14918 AN: 41412

American (AMR) AF: 0.638 AC: 9750 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2279 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2455 AN: 5172

South Asian (SAS) AF: 0.543 AC: 2620 AN: 4822

European-Finnish (FIN) AF: 0.578 AC: 6091 AN: 10542

Middle Eastern (MID) AF: 0.654 AC: 191 AN: 292

European-Non Finnish (NFE) AF: 0.692 AC: 47022 AN: 67964

Other (OTH) AF: 0.593 AC: 1253 AN: 2114

Alfa AF: 0.653 Hom.: 11264

Bravo AF: 0.572

Asia WGS AF: 0.467 AC: 1629 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.69
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2135351; hg19: chr4-113941143;