rs3128651

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.3029A>G(p.Lys1010Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,551,318 control chromosomes in the GnomAD database, including 663,891 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 0.80 ( 51631 hom., cov: 33)

Exomes 𝑓: 0.93 ( 612260 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.598

Publications

21 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=1.9215813E-6).

BP6

Variant 1-225080641-A-G is Benign according to our data. Variant chr1-225080641-A-G is described in ClinVar as [Benign]. Clinvar id is 402647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1 link	c.3029A>G	p.Lys1010Arg	missense_variant	Exon 19 of 86	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH14	ENST00000682510.1 link	c.3029A>G	p.Lys1010Arg	missense_variant	Exon 19 of 86		NM_001367479.1	ENSP00000508305.1	A0A804HLD3
DNAH14	ENST00000430092.5 link	c.3029A>G	p.Lys1010Arg	missense_variant	Exon 19 of 84	5		ENSP00000414402.1	Q0VDD8-4
DNAH14	ENST00000439375.6 link	c.3029A>G	p.Lys1010Arg	missense_variant	Exon 18 of 83	5		ENSP00000392061.2	Q0VDD8-4
DNAH14	ENST00000445597.6 link	c.2831A>G	p.Lys944Arg	missense_variant	Exon 15 of 61	5		ENSP00000409472.2	Q0VDD8-1

Frequencies

GnomAD3 genomes

AF:

0.797

AC:

121026

AN:

151772

Hom.:

51613

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.980

Gnomad AMR

AF:

0.796

Gnomad ASJ

AF:

0.916

Gnomad EAS

AF:

0.715

Gnomad SAS

AF:

0.850

Gnomad FIN

AF:

0.967

Gnomad MID

AF:

0.845

Gnomad NFE

AF:

0.962

Gnomad OTH

AF:

0.822

GnomAD2 exomes

AF:

0.870

AC:

137039

AN:

157606

AF XY:

0.879

show subpopulations

Gnomad AFR exome

AF:

0.471

Gnomad AMR exome

AF:

0.759

Gnomad ASJ exome

AF:

0.928

Gnomad EAS exome

AF:

0.702

Gnomad FIN exome

AF:

0.970

Gnomad NFE exome

AF:

0.960

Gnomad OTH exome

AF:

0.891

GnomAD4 exome

AF:

0.931

AC:

1302573

AN:

1399428

Hom.:

612260

Cov.:

AF XY:

0.931

AC XY:

642580

AN XY:

690206

show subpopulations

African (AFR)

AF:

0.455

AC:

14363

AN:

31572

American (AMR)

AF:

0.766

AC:

27340

AN:

35686

Ashkenazi Jewish (ASJ)

AF:

0.926

AC:

23296

AN:

25162

East Asian (EAS)

AF:

0.738

AC:

26359

AN:

35718

South Asian (SAS)

AF:

0.869

AC:

68807

AN:

79182

European-Finnish (FIN)

AF:

0.968

AC:

47851

AN:

49408

Middle Eastern (MID)

AF:

0.915

AC:

5216

AN:

5700

European-Non Finnish (NFE)

AF:

0.962

AC:

1037402

AN:

1078930

Other (OTH)

AF:

0.894

AC:

51939

AN:

58070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

4544

9088

13633

18177

22721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.797

AC:

121080

AN:

151890

Hom.:

51631

Cov.:

AF XY:

0.797

AC XY:

59182

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.472

AC:

19519

AN:

41378

American (AMR)

AF:

0.796

AC:

12148

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.916

AC:

3178

AN:

3468

East Asian (EAS)

AF:

0.716

AC:

3684

AN:

5148

South Asian (SAS)

AF:

0.852

AC:

4093

AN:

4806

European-Finnish (FIN)

AF:

0.967

AC:

10243

AN:

10588

Middle Eastern (MID)

AF:

0.850

AC:

250

AN:

294

European-Non Finnish (NFE)

AF:

0.962

AC:

65333

AN:

67916

Other (OTH)

AF:

0.823

AC:

1738

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

946

1892

2838

3784

4730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.914

Hom.:

265032

Bravo

AF:

0.769

TwinsUK

AF:

0.960

AC:

3560

ALSPAC

AF:

0.955

AC:

3679

ESP6500AA

AF:

0.519

AC:

718

ESP6500EA

AF:

0.961

AC:

3057

ExAC

AF:

0.859

AC:

21026

Asia WGS

AF:

0.753

AC:

2622

AN:

3478

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

0.068

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.26

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0015

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.24

T;T;.

MetaRNN

Benign

0.0000019

T;T;T

MetaSVM

Benign

-1.0

PhyloP100

-0.60

PrimateAI

Benign

0.31

PROVEAN

Benign

0.050

N;N;N

REVEL

Benign

0.033

Sift

Benign

0.74

T;T;T

Sift4G

Benign

0.52

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.10

ClinPred

0.00057

GERP RS

3.2

Varity_R

0.026

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

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rs3128651

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