rs7535953

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001367479.1(DNAH14):c.11288G>A(p.Arg3763Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,539,904 control chromosomes in the GnomAD database, including 154,539 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18352 hom., cov: 31)

Exomes 𝑓: 0.44 ( 136187 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.104

Publications

14 publications found

Variant links:

Genes affected

DNAH14 (HGNC:2945): (dynein axonemal heavy chain 14) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. Two major classes of dyneins, axonemal and cytoplasmic, have been identified. DNAH14 is an axonemal dynein heavy chain (DHC) (Vaughan et al., 1996 [PubMed 8812413]).[supplied by OMIM, Mar 2008]

DNAH14 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

DNAH14 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=1.3200319E-5).

BP6

Variant 1-225346646-G-A is Benign according to our data. Variant chr1-225346646-G-A is described in ClinVar as [Benign]. Clinvar id is 402660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1 link	c.11288G>A	p.Arg3763Lys	missense_variant	Exon 71 of 86	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1 link	c.11288G>A	p.Arg3763Lys	missense_variant	Exon 71 of 86		NM_001367479.1	ENSP00000508305.1		A0A804HLD3

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73297

AN:

151754

Hom.:

18321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.616

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.507

Gnomad SAS

AF:

0.553

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.461

GnomAD2 exomes

AF:

0.463

AC:

69057

AN:

149002

AF XY:

0.465

show subpopulations

Gnomad AFR exome

AF:

0.627

Gnomad AMR exome

AF:

0.494

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.496

Gnomad FIN exome

AF:

0.365

Gnomad NFE exome

AF:

0.434

Gnomad OTH exome

AF:

0.432

GnomAD4 exome

AF:

0.440

AC:

611174

AN:

1388032

Hom.:

136187

Cov.:

AF XY:

0.444

AC XY:

303773

AN XY:

684808

show subpopulations

African (AFR)

AF:

0.619

AC:

19161

AN:

30954

American (AMR)

AF:

0.485

AC:

16783

AN:

34578

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

8544

AN:

24864

East Asian (EAS)

AF:

0.481

AC:

17122

AN:

35578

South Asian (SAS)

AF:

0.544

AC:

42608

AN:

78298

European-Finnish (FIN)

AF:

0.369

AC:

18112

AN:

49116

Middle Eastern (MID)

AF:

0.417

AC:

1987

AN:

4766

European-Non Finnish (NFE)

AF:

0.430

AC:

461578

AN:

1072414

Other (OTH)

AF:

0.440

AC:

25279

AN:

57464

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

15173

30346

45518

60691

75864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.483

AC:

73375

AN:

151872

Hom.:

18352

Cov.:

AF XY:

0.478

AC XY:

35508

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.616

AC:

25507

AN:

41430

American (AMR)

AF:

0.464

AC:

7074

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

1171

AN:

3460

East Asian (EAS)

AF:

0.506

AC:

2612

AN:

5164

South Asian (SAS)

AF:

0.553

AC:

2662

AN:

4812

European-Finnish (FIN)

AF:

0.354

AC:

3727

AN:

10520

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.428

AC:

29073

AN:

67922

Other (OTH)

AF:

0.464

AC:

980

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1927

3854

5781

7708

9635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.447

Hom.:

45762

Bravo

AF:

0.498

TwinsUK

AF:

0.434

AC:

1608

ALSPAC

AF:

0.434

AC:

1671

ExAC

AF:

0.473

AC:

9945

Asia WGS

AF:

0.539

AC:

1871

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.83

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0046

T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.32

T;T;.

MetaRNN

Benign

0.000013

T;T;T

MetaSVM

Benign

-0.96

PhyloP100

-0.10

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.56

N;N;N

REVEL

Benign

0.022

Sift

Benign

0.087

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

.;B;B

Vest4

0.013

ClinPred

0.0058

GERP RS

-3.8

Varity_R

0.046

Mutation Taster

=100/0

polymorphism (auto)

(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.

rs7535953

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