NM_001386186.2:c.72+82800T>C

Variant names:

• chr4-112789017-T-C
• rs11098171
• NM_001386186.2:c.72+82800T>C

Variant summary

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

The NM_001386186.2(ANK2):​c.72+82800T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 517,422 control chromosomes in the GnomAD database, including 22,738 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 (8634 hom., cov: 32)
  • Exomes 𝑓: 0.25 (14104 hom.)
• Consequence: ANK2 NM_001386186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133
• 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]

RPL7AP30 (HGNC:35757): (ribosomal protein L7a pseudogene 30)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK2	NM_001386186.2	c.72+82800T>C		intron_variant	Intron 1 of 46		NP_001373115.1
ANK2	NM_001386148.2	c.72+82800T>C		intron_variant	Intron 1 of 45		NP_001373077.1
ANK2	NM_001386187.2	c.72+82800T>C		intron_variant	Intron 1 of 42		NP_001373116.1
ANK2	NM_001354269.3	c.72+82800T>C		intron_variant	Intron 1 of 43		NP_001341198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL7AP30	ENST00000482859.1	n.-139A>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47045 AN: 151806 Hom.: 8614 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.248 AC: 90775 AN: 365498 Hom.: 14104 AF XY: 0.246 AC XY: 46641 AN XY: 189752

African (AFR) AF: 0.462 AC: 5018 AN: 10866

American (AMR) AF: 0.384 AC: 5501 AN: 14314

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 1373 AN: 11930

East Asian (EAS) AF: 0.574 AC: 16375 AN: 28510

South Asian (SAS) AF: 0.278 AC: 6488 AN: 23380

European-Finnish (FIN) AF: 0.206 AC: 5204 AN: 25210

Middle Eastern (MID) AF: 0.173 AC: 293 AN: 1690

European-Non Finnish (NFE) AF: 0.199 AC: 45218 AN: 227428

Other (OTH) AF: 0.239 AC: 5305 AN: 22170

GnomAD4 genome AF: 0.310 AC: 47122 AN: 151924 Hom.: 8634 Cov.: 32 AF XY: 0.313 AC XY: 23256 AN XY: 74272

African (AFR) AF: 0.474 AC: 19635 AN: 41382

American (AMR) AF: 0.355 AC: 5415 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3470

East Asian (EAS) AF: 0.581 AC: 3004 AN: 5168

South Asian (SAS) AF: 0.321 AC: 1549 AN: 4820

European-Finnish (FIN) AF: 0.207 AC: 2184 AN: 10546

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14079 AN: 67966

Other (OTH) AF: 0.260 AC: 550 AN: 2112

Alfa AF: 0.241 Hom.: 19159

Bravo AF: 0.331

Asia WGS AF: 0.422 AC: 1465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.77
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs11098171; hg19: chr4-113710173;