Genetic Variant ANKRD17:c.4402-2200G>A (chr4-73104747-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_032217.5(ANKRD17):c.4402-2200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 140,244 control chromosomes in the GnomAD database, including 74 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 0.027 ( 74 hom., cov: 31)

Consequence

ANKRD17
NM_032217.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.77

Publications

2 publications found

Variant links:

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

ANKRD17 links:

ENSG00000303699 (HGNC:):

ENSG00000303699 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0272 (3818/140244) while in subpopulation AFR AF = 0.0411 (1523/37040). AF 95% confidence interval is 0.0394. There are 74 homozygotes in GnomAd4. There are 1853 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 3818 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD17	NM_032217.5 link	c.4402-2200G>A		intron_variant	Intron 24 of 33	ENST00000358602.9	NP_115593.3	O75179-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD17	ENST00000358602.9 link	c.4402-2200G>A		intron_variant	Intron 24 of 33	5	NM_032217.5	ENSP00000351416.4		O75179-1

Frequencies

GnomAD3 genomes

AF:

0.0272

AC:

3812

AN:

140152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0411

Gnomad AMI

AF:

0.0324

Gnomad AMR

AF:

0.0247

Gnomad ASJ

AF:

0.0425

Gnomad EAS

AF:

0.00236

Gnomad SAS

AF:

0.0287

Gnomad FIN

AF:

0.0210

Gnomad MID

AF:

0.0235

Gnomad NFE

AF:

0.0215

Gnomad OTH

AF:

0.0286

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

GnomAD4 genome

AF:

0.0272

AC:

3818

AN:

140244

Hom.:

Cov.:

AF XY:

0.0274

AC XY:

1853

AN XY:

67686

show subpopulations

African (AFR)

AF:

0.0411

AC:

1523

AN:

37040

American (AMR)

AF:

0.0247

AC:

340

AN:

13770

Ashkenazi Jewish (ASJ)

AF:

0.0425

AC:

144

AN:

3392

East Asian (EAS)

AF:

0.00237

AC:

AN:

4642

South Asian (SAS)

AF:

0.0290

AC:

126

AN:

4342

European-Finnish (FIN)

AF:

0.0210

AC:

183

AN:

8734

Middle Eastern (MID)

AF:

0.0254

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.0215

AC:

1402

AN:

65274

Other (OTH)

AF:

0.0283

AC:

AN:

1910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

171

342

512

683

854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0214

Hom.:

Bravo

AF:

0.0263

Asia WGS

AF:

0.0320

AC:

111

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.20

(source)

DANN

Benign

0.25

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over