16-70938692-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001270974.2(HYDIN):c.6917A>G(p.Glu2306Gly) variant causes a missense change. The variant allele was found at a frequency of 0.693 in 1,612,490 control chromosomes in the GnomAD database, including 402,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 28289 hom., cov: 32)

Exomes 𝑓: 0.71 ( 374452 hom. )

Consequence

HYDIN
NM_001270974.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.29

Publications

25 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.3903714E-6).

BP6

Variant 16-70938692-T-C is Benign according to our data. Variant chr16-70938692-T-C is described in ClinVar as Benign. ClinVar VariationId is 402955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYDIN	NM_001270974.2 link	c.6917A>G	p.Glu2306Gly	missense_variant	Exon 44 of 86	ENST00000393567.7	NP_001257903.1	Q4G0P3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYDIN	ENST00000393567.7 link	c.6917A>G	p.Glu2306Gly	missense_variant	Exon 44 of 86	5	NM_001270974.2	ENSP00000377197.2		Q4G0P3-1
HYDIN	ENST00000309900.11 link	n.1437A>G		non_coding_transcript_exon_variant	Exon 9 of 20	1

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

86938

AN:

151788

Hom.:

28284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.812

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.661

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.754

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.751

Gnomad OTH

AF:

0.597

GnomAD2 exomes

AF:

0.612

AC:

152378

AN:

249038

AF XY:

0.624

show subpopulations

Gnomad AFR exome

AF:

0.270

Gnomad AMR exome

AF:

0.382

Gnomad ASJ exome

AF:

0.665

Gnomad EAS exome

AF:

0.444

Gnomad FIN exome

AF:

0.756

Gnomad NFE exome

AF:

0.750

Gnomad OTH exome

AF:

0.654

GnomAD4 exome

AF:

0.705

AC:

1029903

AN:

1460584

Hom.:

374452

Cov.:

AF XY:

0.701

AC XY:

509502

AN XY:

726672

show subpopulations

African (AFR)

AF:

0.260

AC:

8703

AN:

33452

American (AMR)

AF:

0.394

AC:

17630

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.665

AC:

17384

AN:

26126

East Asian (EAS)

AF:

0.432

AC:

17160

AN:

39688

South Asian (SAS)

AF:

0.510

AC:

44012

AN:

86214

European-Finnish (FIN)

AF:

0.759

AC:

40400

AN:

53254

Middle Eastern (MID)

AF:

0.664

AC:

3824

AN:

5762

European-Non Finnish (NFE)

AF:

0.757

AC:

840525

AN:

1111044

Other (OTH)

AF:

0.667

AC:

40265

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

13597

27194

40791

54388

67985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19988

39976

59964

79952

99940

<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:

0.573

AC:

86970

AN:

151906

Hom.:

28289

Cov.:

AF XY:

0.568

AC XY:

42182

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.271

AC:

11233

AN:

41472

American (AMR)

AF:

0.503

AC:

7684

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.661

AC:

2293

AN:

3470

East Asian (EAS)

AF:

0.432

AC:

2225

AN:

5150

South Asian (SAS)

AF:

0.506

AC:

2435

AN:

4808

European-Finnish (FIN)

AF:

0.754

AC:

7974

AN:

10570

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.751

AC:

50939

AN:

67856

Other (OTH)

AF:

0.599

AC:

1260

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1567

3134

4702

6269

7836

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.649

Hom.:

51152

Bravo

AF:

0.542

ExAC

AF:

0.614

AC:

74225

Asia WGS

AF:

0.448

AC:

1556

AN:

3476

EpiCase

AF:

0.737

EpiControl

AF:

0.742

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 20, 2022

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Primary ciliary dyskinesia 5

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.97

MetaRNN

Benign

0.0000034

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

PhyloP100

6.3

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-5.2

REVEL

Benign

0.24

Sift

Uncertain

0.0030

Vest4

0.27

ClinPred

0.018

GERP RS

5.6

Varity_R

0.34

gMVP

0.23

Mutation Taster

=97/3

polymorphism (auto)

(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