dbSNP rs397515414: HYDIN:p.Lys308* (chr16-71137272-T-A) – ACMG Classification: Pathogenic (11 pts)

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_001270974.2(HYDIN):c.922A>T(p.Lys308*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HYDIN
NM_001270974.2 stop_gained

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.70

Publications

3 publications found

Variant links:

Genes affected

HYDIN (HGNC:19368): (HYDIN axonemal central pair apparatus protein) This gene encodes a protein that may be involved in cilia motility. Mutations in this gene cause of autosomal recessive primary ciliary dyskinesia-5, a disorder characterized by the accumulation of cerebrospinal fluid within the ventricles of the brain. A duplicate copy of this gene has been found in humans on chromosome 1. [provided by RefSeq, Jan 2013]

HYDIN Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 5
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, ClinGen, G2P
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

HYDIN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 16-71137272-T-A is Pathogenic according to our data. Variant chr16-71137272-T-A is described in ClinVar as Pathogenic. ClinVar VariationId is 39699.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYDIN	NM_001270974.2 link	c.922A>T	p.Lys308*	stop_gained	Exon 8 of 86	ENST00000393567.7	NP_001257903.1	Q4G0P3-1
HYDIN	NM_017558.5 link	c.922A>T	p.Lys308*	stop_gained	Exon 8 of 20		NP_060028.2	Q4G0P3-5
HYDIN	NM_001198542.1 link	c.1003A>T	p.Lys335*	stop_gained	Exon 8 of 19		NP_001185471.1	Q4G0P3-8
HYDIN	NM_001198543.1 link	c.973A>T	p.Lys325*	stop_gained	Exon 8 of 19		NP_001185472.1	Q4G0P3-10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYDIN	ENST00000393567.7 link	c.922A>T	p.Lys308*	stop_gained	Exon 8 of 86	5	NM_001270974.2	ENSP00000377197.2		Q4G0P3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000185

AC:

AN:

539810

Hom.:

Cov.:

AF XY:

0.00000348

AC XY:

AN XY:

287208

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

14660

American (AMR)

AF:

0.00

AC:

AN:

28060

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16606

East Asian (EAS)

AF:

0.00

AC:

AN:

32568

South Asian (SAS)

AF:

0.00

AC:

AN:

52946

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2370

European-Non Finnish (NFE)

AF:

0.00000304

AC:

AN:

329190

Other (OTH)

AF:

0.00

AC:

AN:

29488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 5

Pathogenic:1

Oct 05, 2012

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.62

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.99

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.93

PhyloP100

4.7

Vest4

0.42

ClinPred

1.0

GERP RS

4.5

Mutation Taster

=1/199

disease causing (ClinVar)

(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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over