Genetic Variant ANKDD1B:p.Gln462* (chr5-75666984-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_001276713.2(ANKDD1B):c.1384C>T(p.Gln462*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000406 in 1,477,880 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00039 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 5 hom. )

Consequence

ANKDD1B
NM_001276713.2 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.16

Publications

3 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 -12 ACMG points.

BP6

Variant 5-75666984-C-T is Benign according to our data. Variant chr5-75666984-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 734732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 60 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.1384C>T	p.Gln462*	stop_gained	Exon 12 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.1384C>T	p.Gln462*	stop_gained	Exon 12 of 14	ENSP00000471417.1	A6NHY2
ANKDD1B	ENST00000506596.6	TSL:1	n.640C>T		non_coding_transcript_exon	Exon 4 of 6
ANKDD1B	ENST00000885189.1		c.1519C>T	p.Gln507*	stop_gained	Exon 12 of 14	ENSP00000555248.1

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00789

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000802

AC:

AN:

83506

AF XY:

0.000954

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000249

Gnomad ASJ exome

AF:

0.000307

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000335

Gnomad OTH exome

AF:

0.000751

GnomAD4 exome

AF:

0.000407

AC:

540

AN:

1325628

Hom.:

Cov.:

AF XY:

0.000547

AC XY:

355

AN XY:

648474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29730

American (AMR)

AF:

0.000257

AC:

AN:

27186

Ashkenazi Jewish (ASJ)

AF:

0.000193

AC:

AN:

20734

East Asian (EAS)

AF:

0.00

AC:

AN:

35420

South Asian (SAS)

AF:

0.00517

AC:

349

AN:

67480

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31488

Middle Eastern (MID)

AF:

0.00670

AC:

AN:

5374

European-Non Finnish (NFE)

AF:

0.000108

AC:

114

AN:

1052722

Other (OTH)

AF:

0.000541

AC:

AN:

55494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

113

141

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:

0.000394

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41554

American (AMR)

AF:

0.000196

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00831

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.000108

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.00133

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.57

CADD

Pathogenic

(source)

DANN

Benign

0.69

FATHMM_MKL

Uncertain

0.90

PhyloP100

5.2

Vest4

0.20

GERP RS

4.2

Mutation Taster

=88/112

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over