rs1196149362

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2

The NM_032217.5(ANKRD17):c.7470C>A(p.Asp2490Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ANKRD17
NM_032217.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.739

Publications

0 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):

syndromic complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Chopra-Amiel-Gordon syndrome
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ANKRD17 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.078551024).

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0000205 (30/1461408) while in subpopulation NFE AF = 0.0000261 (29/1111768). AF 95% confidence interval is 0.0000183. There are 0 homozygotes in GnomAdExome4. There are 13 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAdExome4 at 30 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD17	NM_032217.5	MANE Select	c.7470C>A	p.Asp2490Glu	missense	Exon 32 of 34	NP_115593.3
ANKRD17	NM_015574.2		c.7467C>A	p.Asp2489Glu	missense	Exon 32 of 34	NP_056389.1	O75179-2
ANKRD17	NM_001286771.3		c.7131C>A	p.Asp2377Glu	missense	Exon 32 of 34	NP_001273700.1	O75179-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD17	ENST00000358602.9	TSL:5 MANE Select	c.7470C>A	p.Asp2490Glu	missense	Exon 32 of 34	ENSP00000351416.4	O75179-1
ANKRD17	ENST00000509867.6	TSL:1	c.7131C>A	p.Asp2377Glu	missense	Exon 32 of 34	ENSP00000427151.2	O75179-7
ANKRD17	ENST00000558247.5	TSL:1	c.7119C>A	p.Asp2373Glu	missense	Exon 32 of 34	ENSP00000453434.1	H0YM23

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251106

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461408

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726986

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39628

South Asian (SAS)

AF:

0.00

AC:

AN:

86204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000261

AC:

AN:

1111768

Other (OTH)

AF:

0.0000166

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000508

Hom.:

Bravo

AF:

0.0000151

EpiCase

AF:

0.0000548

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.10

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0080

MetaRNN

Benign

0.079

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.65

PhyloP100

0.74

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.1

REVEL

Benign

0.11

Sift

Benign

0.079

Sift4G

Benign

0.90

Polyphen

0.043

Vest4

0.14

MutPred

0.15

Gain of loop (P = 0.0851)

MVP

0.37

MPC

0.28

ClinPred

0.065

GERP RS

0.20

Varity_R

0.084

gMVP

0.78

Mutation Taster

=69/31

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over