rs10014072

Positions:

• chr4-113027634-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386142.1(ANK2):​c.21+123120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 151,916 control chromosomes in the GnomAD database, including 32,363 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 0.65 (32363 hom., cov: 32)
• Consequence: ANK2 NM_001386142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

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]

LOC124900761 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK2	NM_001386142.1	c.21+123120A>G		intron_variant			NP_001373071.1
ANK2	NM_001386143.1	c.21+123120A>G		intron_variant			NP_001373072.1
ANK2	NM_001386186.2	c.73-146782A>G		intron_variant			NP_001373115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK2	ENST00000506722.5	c.21+123120A>G		intron_variant		1		ENSP00000421067.1
ANK2	ENST00000672209.1	c.21+123120A>G		intron_variant				ENSP00000499982.1
ANK2	ENST00000673298.1	c.21+123120A>G		intron_variant				ENSP00000500245.1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98490 AN: 151798 Hom.: 32336 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.649 AC: 98559 AN: 151916 Hom.: 32363 Cov.: 32 AF XY: 0.647 AC XY: 48018 AN XY: 74252

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.641

Alfa AF: 0.687 Hom.: 38715

Bravo AF: 0.654

Asia WGS AF: 0.539 AC: 1878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.94
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10014072; hg19: chr4-113948790;