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
• Publications: 21 publications found

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]

ANKRD17 Gene-Disease associations (from GenCC):

• Chopra-Amiel-Gordon syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AD Classification: STRONG Submitted by: ClinGen

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032217.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD17	NM_032217.5	MANE Select	c.7731G>A	p.Thr2577Thr	synonymous	Exon 33 of 34	NP_115593.3
	ANKRD17	NM_015574.2		c.7728G>A	p.Thr2576Thr	synonymous	Exon 33 of 34	NP_056389.1
	ANKRD17	NM_001286771.3		c.7392G>A	p.Thr2464Thr	synonymous	Exon 33 of 34	NP_001273700.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD17	ENST00000358602.9	TSL:5 MANE Select	c.7731G>A	p.Thr2577Thr	synonymous	Exon 33 of 34	ENSP00000351416.4
	ANKRD17	ENST00000509867.6	TSL:1	c.7392G>A	p.Thr2464Thr	synonymous	Exon 33 of 34	ENSP00000427151.2
	ANKRD17	ENST00000558247.5	TSL:1	c.7380G>A	p.Thr2460Thr	synonymous	Exon 33 of 34	ENSP00000453434.1

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

African (AFR) AF: 0.0337 AC: 1124 AN: 33314

American (AMR) AF: 0.238 AC: 10458 AN: 43892

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4610 AN: 26018

East Asian (EAS) AF: 0.287 AC: 11356 AN: 39606

South Asian (SAS) AF: 0.217 AC: 18514 AN: 85238

European-Finnish (FIN) AF: 0.101 AC: 5416 AN: 53374

Middle Eastern (MID) AF: 0.204 AC: 1173 AN: 5754

European-Non Finnish (NFE) AF: 0.161 AC: 179082 AN: 1110652

Other (OTH) 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

African (AFR) AF: 0.0387 AC: 1606 AN: 41514

American (AMR) AF: 0.211 AC: 3217 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 628 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1412 AN: 5148

South Asian (SAS) AF: 0.224 AC: 1082 AN: 4820

European-Finnish (FIN) AF: 0.0946 AC: 1000 AN: 10570

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10812 AN: 67994

Other (OTH) AF: 0.159 AC: 337 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	6.4
DANN	Benign	0.68
PhyloP100		0.20
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

Other links and lift over

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