rs2285711

Variant names:

• chr4-113196124-A-G
• rs2285711
• NM_001148.6:c.187-244A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-113196124-A-G
• chr4-113196124-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001148.6(ANK2):​c.187-244A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,214 control chromosomes in the GnomAD database, including 2,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2318 hom., cov: 33)
• Consequence: ANK2 NM_001148.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0410
• Publications: 2 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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen, Ambry Genetics
• Brugada syndrome

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp
• catecholaminergic polymorphic ventricular tachycardia

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, ClinGen
• heart conduction disease

  Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• cardiac arrhythmia, ankyrin-B-related

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• long QT syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-113196124-A-G is Benign according to our data. Variant chr4-113196124-A-G is described in ClinVar as Benign. ClinVar VariationId is 1248503.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001148.6. 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_001148.6	MANE Select	c.187-244A>G		intron	N/A	NP_001139.3
	ANK2	NM_001386174.1		c.238-244A>G		intron	N/A	NP_001373103.1	H0Y933
	ANK2	NM_001386175.1		c.238-244A>G		intron	N/A	NP_001373104.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK2	ENST00000357077.9	TSL:1 MANE Select	c.187-244A>G		intron	N/A	ENSP00000349588.4	Q01484-4
	ANK2	ENST00000506344.6	TSL:1	c.238-244A>G		intron	N/A	ENSP00000422888.2	H0Y933
	ANK2	ENST00000394537.7	TSL:1	c.187-244A>G		intron	N/A	ENSP00000378044.3	Q01484-2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26134 AN: 152096 Hom.: 2317 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.172 AC: 26157 AN: 152214 Hom.: 2318 Cov.: 33 AF XY: 0.176 AC XY: 13098 AN XY: 74412

African (AFR) AF: 0.194 AC: 8037 AN: 41526

American (AMR) AF: 0.143 AC: 2188 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 610 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1352 AN: 5186

South Asian (SAS) AF: 0.139 AC: 674 AN: 4832

European-Finnish (FIN) AF: 0.241 AC: 2546 AN: 10582

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10202 AN: 68016

Other (OTH) AF: 0.164 AC: 347 AN: 2112

Alfa AF: 0.159 Hom.: 251

Bravo AF: 0.168

Asia WGS AF: 0.171 AC: 593 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.73
PhyloP100		0.041
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2285711;

hg19: chr4-114117280;