4-113007318-G-C

Variant names:

• chr4-113007318-G-C
• rs1532876
• ENST00000506722.5:c.21+102804G>C

Variant summary

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

The ENST00000506722.5(ANK2):​c.21+102804G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,230 control chromosomes in the GnomAD database, including 61,507 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 0.90 (61507 hom., cov: 32)
• Consequence: ANK2 ENST00000506722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK2	NM_001386142.1	c.21+102804G>C		intron_variant	Intron 2 of 44		NP_001373071.1
ANK2	NM_001386143.1	c.21+102804G>C		intron_variant	Intron 2 of 47		NP_001373072.1
ANK2	NM_001386186.2	c.73-167098G>C		intron_variant	Intron 1 of 46		NP_001373115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK2	ENST00000506722.5	c.21+102804G>C		intron_variant	Intron 2 of 46	1		ENSP00000421067.1
ANK2	ENST00000672209.1	c.21+102804G>C		intron_variant	Intron 2 of 47			ENSP00000499982.1
ANK2	ENST00000673298.1	c.21+102804G>C		intron_variant	Intron 2 of 46			ENSP00000500245.1

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136416 AN: 152112 Hom.: 61444 Cov.: 32

Gnomad AFR AF: 0.973

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.933

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.905

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

GnomAD4 genome AF: 0.897 AC: 136538 AN: 152230 Hom.: 61507 Cov.: 32 AF XY: 0.900 AC XY: 66972 AN XY: 74430

African (AFR) AF: 0.974 AC: 40453 AN: 41552

American (AMR) AF: 0.933 AC: 14276 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 3005 AN: 3472

East Asian (EAS) AF: 0.989 AC: 5109 AN: 5168

South Asian (SAS) AF: 0.918 AC: 4427 AN: 4820

European-Finnish (FIN) AF: 0.852 AC: 9024 AN: 10590

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.842 AC: 57257 AN: 68018

Other (OTH) AF: 0.906 AC: 1912 AN: 2110

Alfa AF: 0.808 Hom.: 2425

Bravo AF: 0.909

Asia WGS AF: 0.953 AC: 3316 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	0.32
DANN	Benign	0.69
PhyloP100		-0.41
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: rs1532876; hg19: chr4-113928474;