chr16-71186765-C-T

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.131G>A(p.Arg44Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00433 in 1,610,892 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 25 hom. )

Consequence

HYDIN
NM_001270974.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: -1.69

Publications

8 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=0.002897948).

BP6

Variant 16-71186765-C-T is Benign according to our data. Variant chr16-71186765-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 547951.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00359 (547/152202) while in subpopulation NFE AF = 0.00494 (336/67990). AF 95% confidence interval is 0.00451. There are 3 homozygotes in GnomAd4. There are 251 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYDIN	NM_001270974.2 link	c.131G>A	p.Arg44Gln	missense_variant	Exon 2 of 86	ENST00000393567.7	NP_001257903.1	Q4G0P3-1
HYDIN	NM_017558.5 link	c.131G>A	p.Arg44Gln	missense_variant	Exon 2 of 20		NP_060028.2	Q4G0P3-5
HYDIN	NM_001198542.1 link	c.212G>A	p.Arg71Gln	missense_variant	Exon 2 of 19		NP_001185471.1	Q4G0P3-8
HYDIN	NM_001198543.1 link	c.182G>A	p.Arg61Gln	missense_variant	Exon 2 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.131G>A	p.Arg44Gln	missense_variant	Exon 2 of 86	5	NM_001270974.2	ENSP00000377197.2		Q4G0P3-1

Frequencies

GnomAD3 genomes

AF:

0.00360

AC:

547

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00494

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00349

AC:

867

AN:

248642

AF XY:

0.00336

show subpopulations

Gnomad AFR exome

AF:

0.000989

Gnomad AMR exome

AF:

0.00158

Gnomad ASJ exome

AF:

0.0205

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00427

Gnomad NFE exome

AF:

0.00428

Gnomad OTH exome

AF:

0.00347

GnomAD4 exome

AF:

0.00441

AC:

6429

AN:

1458690

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

3077

AN XY:

725698

show subpopulations

African (AFR)

AF:

0.000780

AC:

AN:

33348

American (AMR)

AF:

0.00149

AC:

AN:

44430

Ashkenazi Jewish (ASJ)

AF:

0.0215

AC:

560

AN:

26024

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39644

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85752

European-Finnish (FIN)

AF:

0.00399

AC:

213

AN:

53348

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00476

AC:

5280

AN:

1110124

Other (OTH)

AF:

0.00466

AC:

281

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

285

570

856

1141

1426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

208

416

624

832

1040

<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:

0.00359

AC:

547

AN:

152202

Hom.:

Cov.:

AF XY:

0.00337

AC XY:

251

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.000866

AC:

AN:

41552

American (AMR)

AF:

0.00144

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0245

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00349

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00494

AC:

336

AN:

67990

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00505

Hom.:

Bravo

AF:

0.00365

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00430

AC:

ExAC

AF:

0.00306

AC:

371

EpiCase

AF:

0.00366

EpiControl

AF:

0.00440

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

HYDIN: BP4, BS2 -

Primary ciliary dyskinesia 5

Uncertain:1Benign:1

Apr 23, 2020

Genetics and Molecular Pathology, SA Pathology

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 12, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

HYDIN-related disorder

Benign:1

May 11, 2023

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.5

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.023

T;.;.;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0058

M_CAP

Benign

0.0025

MetaRNN

Benign

0.0029

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.41

N;N;.;.;.

PhyloP100

-1.7

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.070

N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.61

T;T;T;T;T

Sift4G

Benign

0.15

.;T;T;T;T

Polyphen

0.0020, 0.0030

.;B;.;.;B

Vest4

0.10

MVP

0.11

ClinPred

0.00096

GERP RS

-7.8

Varity_R

0.025

gMVP

0.20

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over