4-73076961-C-T

Variant names:

• chr4-73076961-C-T
• rs2306058
• NM_032217.5:c.7731G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_032217.5(ANKRD17):​c.7731G>A​(p.Thr2577Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,610,202 control chromosomes in the GnomAD database, including 23,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1772 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21695 hom.)
• Consequence: ANKRD17 NM_032217.5 synonymous
• Clinical Significance: association criteria provided, single submitter O:1
• Conservation: PhyloP100: 0.200

Genes affected

ANKRD17 (HGNC:23575): (ankyrin repeat domain 17) The protein encoded by this gene belongs to the family of ankyrin repeat-containing proteins, and contains two distinct arrays of ankyrin repeats in its amino-terminal region, one with 15 ankyrin repeats, and the other with 10 ankyrin repeats. It also contains a nuclear export signal, nuclear localization signal, and a cyclin-binding RXL motif. Localization of this protein to the nucleus has been shown experimentally, and interactions between this protein and cyclin-dependent kinase 2 have been observed. It has been suggested that this protein plays a role in both DNA replication and in both anti-viral and anti-bacterial innate immune pathways. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP7: Synonymous conserved (PhyloP=0.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD17	NM_032217.5	c.7731G>A	p.Thr2577Thr	synonymous_variant	Exon 33 of 34	ENST00000358602.9	NP_115593.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD17	ENST00000358602.9	c.7731G>A	p.Thr2577Thr	synonymous_variant	Exon 33 of 34	5	NM_032217.5	ENSP00000351416.4
ANKRD17	ENST00000509867.6	c.7392G>A	p.Thr2464Thr	synonymous_variant	Exon 33 of 34	1		ENSP00000427151.2
ANKRD17	ENST00000558247.5	c.7380G>A	p.Thr2460Thr	synonymous_variant	Exon 33 of 34	1		ENSP00000453434.1
ANKRD17	ENST00000330838.10	c.6978G>A	p.Thr2326Thr	synonymous_variant	Exon 32 of 33	2		ENSP00000332265.6

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20400 AN: 151988 Hom.: 1773 Cov.: 32

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.0946

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.160

GnomAD2 exomes AF: 0.175 AC: 43323 AN: 247888 AF XY: 0.176

Gnomad AFR exome AF: 0.0350

Gnomad AMR exome AF: 0.242

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.260

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.172

GnomAD4 exome AF: 0.166 AC: 242336 AN: 1458096 Hom.: 21695 Cov.: 32 AF XY: 0.167 AC XY: 121226 AN XY: 725198

Gnomad4 AFR exome AF: 0.0337 AC: 1124 AN: 33314

Gnomad4 AMR exome AF: 0.238 AC: 10458 AN: 43892

Gnomad4 ASJ exome AF: 0.177 AC: 4610 AN: 26018

Gnomad4 EAS exome AF: 0.287 AC: 11356 AN: 39606

Gnomad4 SAS exome AF: 0.217 AC: 18514 AN: 85238

Gnomad4 FIN exome AF: 0.101 AC: 5416 AN: 53374

Gnomad4 NFE exome AF: 0.161 AC: 179082 AN: 1110652

Gnomad4 Remaining exome AF: 0.176 AC: 10603 AN: 60248

GnomAD4 genome AF: 0.134 AC: 20395 AN: 152106 Hom.: 1772 Cov.: 32 AF XY: 0.134 AC XY: 9996 AN XY: 74350

Gnomad4 AFR AF: 0.0387 AC: 0.0386857 AN: 0.0386857

Gnomad4 AMR AF: 0.211 AC: 0.210619 AN: 0.210619

Gnomad4 ASJ AF: 0.181 AC: 0.18098 AN: 0.18098

Gnomad4 EAS AF: 0.274 AC: 0.274281 AN: 0.274281

Gnomad4 SAS AF: 0.224 AC: 0.224481 AN: 0.224481

Gnomad4 FIN AF: 0.0946 AC: 0.0946074 AN: 0.0946074

Gnomad4 NFE AF: 0.159 AC: 0.159014 AN: 0.159014

Gnomad4 OTH AF: 0.159 AC: 0.159413 AN: 0.159413

Alfa AF: 0.161 Hom.: 4166

Bravo AF: 0.139

Asia WGS AF: 0.266 AC: 928 AN: 3478

EpiCase AF: 0.174

EpiControl AF: 0.168

ClinVar

Significance: association

Submissions summary: Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lip and oral cavity carcinoma Other:1

-

Department of Biological Science, Sunandan Divatia School of Science, NMIMS University

Significance: association

Review Status: criteria provided, single submitter

Collection Method: case-control

A significant association of rs2306058 (ANKRD17) CT (odds ratio [OR] 0.72; 95% confidence interval [CI] 0.56-0.93) indicated decreased risk to oral cancer. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	6.4
DANN	Benign	0.68
Mutation Taster		=91/9	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

Publications

LitVar

Other links and lift over

dbSNP: rs2306058; hg19: chr4-73942678; COSMIC: COSV58220466; COSMIC: COSV58220466;