Genetic Variant ANKDD1B:p.Asp2Glu (chr5-75611640-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001276713.2(ANKDD1B):c.6C>A(p.Asp2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000317 in 1,231,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

ANKDD1B
NM_001276713.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.920

Publications

0 publications found

Variant links:

Genes affected

ANKDD1B (HGNC:32525): (ankyrin repeat and death domain containing 1B) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ANKDD1B Gene-Disease associations (from GenCC):

ankylosing spondylitis
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ANKDD1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.060549825).

BS2

High AC in GnomAdExome4 at 38 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276713.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKDD1B	NM_001276713.2	MANE Select	c.6C>A	p.Asp2Glu	missense	Exon 1 of 14	NP_001263642.1	A6NHY2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKDD1B	ENST00000601380.4	TSL:5 MANE Select	c.6C>A	p.Asp2Glu	missense	Exon 1 of 14	ENSP00000471417.1	A6NHY2
ANKDD1B	ENST00000885189.1		c.6C>A	p.Asp2Glu	missense	Exon 1 of 14	ENSP00000555248.1
ANKDD1B	ENST00000885191.1		c.6C>A	p.Asp2Glu	missense	Exon 1 of 12	ENSP00000555250.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151916

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000352

AC:

AN:

1079324

Hom.:

Cov.:

AF XY:

0.0000432

AC XY:

AN XY:

509634

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22936

American (AMR)

AF:

0.00

AC:

AN:

8402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14364

East Asian (EAS)

AF:

0.00

AC:

AN:

26516

South Asian (SAS)

AF:

0.00

AC:

AN:

19490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21108

Middle Eastern (MID)

AF:

0.000343

AC:

AN:

2914

European-Non Finnish (NFE)

AF:

0.0000402

AC:

AN:

919952

Other (OTH)

AF:

0.00

AC:

AN:

43642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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:

0.00000658

AC:

AN:

151916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41306

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.55

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.0045

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.19

M_CAP

Benign

0.026

MetaRNN

Benign

0.061

MutationAssessor

Benign

0.0

PhyloP100

-0.92

PrimateAI

Uncertain

0.69

Sift4G

Pathogenic

0.0

Vest4

0.039

MVP

0.34

GERP RS

-0.055

PromoterAI

0.034

Neutral

(source)

Varity_R

0.036

gMVP

0.042

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over