chr5-75666984-C-T

Position:

• chr5-75666984-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001276713.2(ANKDD1B):​c.1384C>T​(p.Gln462Ter) 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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.16

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 734732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKDD1B	NM_001276713.2	c.1384C>T	p.Gln462Ter	stop_gained	12/14	ENST00000601380.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKDD1B	ENST00000601380.4	c.1384C>T	p.Gln462Ter	stop_gained	12/14	5	NM_001276713.2	P1

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 58 AN: 152136 Hom.: 2 Cov.: 32

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

GnomAD3 exomes AF: 0.000802 AC: 67 AN: 83506 Hom.: 0 AF XY: 0.000954 AC XY: 41 AN XY: 42960

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 SAS exome AF: 0.00490

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.: 5 Cov.: 30 AF XY: 0.000547 AC XY: 355 AN XY: 648474

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000257

Gnomad4 ASJ exome AF: 0.000193

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00517

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000108

Gnomad4 OTH exome AF: 0.000541

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152252 Hom.: 2 Cov.: 32 AF XY: 0.000564 AC XY: 42 AN XY: 74424

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00831

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000168 Hom.: 0

Bravo AF: 0.000140

ExAC AF: 0.00133 AC: 26

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	38
DANN	Benign	0.69
FATHMM_MKL	Uncertain	0.90	D
Vest4		0.20
GERP RS		4.2

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

LitVar

Other links and lift over

dbSNP: rs534392284; hg19: chr5-74962809;