rs6850768

Positions:

• chr4-112797744-C-T

Variant summary

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

The NM_001386186.2(ANK2):​c.72+91527C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 172,086 control chromosomes in the GnomAD database, including 8,289 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 0.31 (7593 hom., cov: 32)
  • Exomes 𝑓: 0.26 (696 hom.)
• Consequence: ANK2 NM_001386186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

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]

ENSG00000250500 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK2	NM_001386186.2	c.72+91527C>T		intron_variant			NP_001373115.1
ANK2	NM_001386148.2	c.72+91527C>T		intron_variant			NP_001373077.1
ANK2	NM_001386187.2	c.72+91527C>T		intron_variant			NP_001373116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000250500	ENST00000503353.1	n.658G>A		non_coding_transcript_exon_variant	2/2	6

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47512 AN: 151858 Hom.: 7575 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.262 AC: 5261 AN: 20110 Hom.: 696 Cov.: 0 AF XY: 0.265 AC XY: 3153 AN XY: 11878

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.314

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.313 AC: 47562 AN: 151976 Hom.: 7593 Cov.: 32 AF XY: 0.315 AC XY: 23354 AN XY: 74250

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.343

Alfa AF: 0.295 Hom.: 1608

Bravo AF: 0.316

Asia WGS AF: 0.392 AC: 1363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.5
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6850768; hg19: chr4-113718900;