rs79607350

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001270974.2(HYDIN):c.14857C>T(p.Arg4953Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,613,950 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 41 hom. )

Consequence

HYDIN
NM_001270974.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 7.47

Publications

7 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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009678125).

BP6

Variant 16-70809809-G-A is Benign according to our data. Variant chr16-70809809-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 445775.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00266 (405/152316) while in subpopulation SAS AF = 0.0166 (80/4816). AF 95% confidence interval is 0.0137. There are 2 homozygotes in GnomAd4. There are 207 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYDIN	NM_001270974.2 link	c.14857C>T	p.Arg4953Trp	missense_variant	Exon 85 of 86	ENST00000393567.7	NP_001257903.1	Q4G0P3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HYDIN	ENST00000393567.7 link	c.14857C>T	p.Arg4953Trp	missense_variant	Exon 85 of 86	5	NM_001270974.2	ENSP00000377197.2	Q4G0P3-1
HYDIN	ENST00000378856.8 link	n.*3737C>T		non_coding_transcript_exon_variant	Exon 21 of 22	1		ENSP00000463350.1	J3QL30
HYDIN	ENST00000378856.8 link	n.*3737C>T		3_prime_UTR_variant	Exon 21 of 22	1		ENSP00000463350.1	J3QL30

Frequencies

GnomAD3 genomes

AF:

0.00267

AC:

406

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00500

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00320

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.00426

AC:

1063

AN:

249564

AF XY:

0.00498

show subpopulations

Gnomad AFR exome

AF:

0.000904

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.00451

Gnomad FIN exome

AF:

0.000464

Gnomad NFE exome

AF:

0.00361

Gnomad OTH exome

AF:

0.00363

GnomAD4 exome

AF:

0.00412

AC:

6020

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

3273

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.000687

AC:

AN:

33472

American (AMR)

AF:

0.00186

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00233

AC:

AN:

26132

East Asian (EAS)

AF:

0.00275

AC:

109

AN:

39698

South Asian (SAS)

AF:

0.0153

AC:

1322

AN:

86256

European-Finnish (FIN)

AF:

0.000543

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00868

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00364

AC:

4048

AN:

1111790

Other (OTH)

AF:

0.00489

AC:

295

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

326

652

977

1303

1629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<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:

0.00266

AC:

405

AN:

152316

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000698

AC:

AN:

41572

American (AMR)

AF:

0.00235

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3468

East Asian (EAS)

AF:

0.00501

AC:

AN:

5186

South Asian (SAS)

AF:

0.0166

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00320

AC:

218

AN:

68036

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00353

Hom.:

Bravo

AF:

0.00258

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000511

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00474

AC:

573

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.00349

EpiControl

AF:

0.00379

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

HYDIN: BP4, BS1, BS2 -

May 30, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 5

Uncertain:1

Oct 03, 2019

Genetics and Molecular Pathology, SA Pathology

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.41

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Uncertain

0.96

MetaRNN

Benign

0.0097

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

PhyloP100

7.5

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-6.4

REVEL

Uncertain

0.31

Sift

Uncertain

0.0010

Vest4

0.68

MVP

0.38

ClinPred

0.058

GERP RS

5.9

Varity_R

0.38

gMVP

0.36

Mutation Taster

=83/17

polymorphism

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over