rs115366080

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001367479.1(DNAH14):c.2792C>A(p.Ala931Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 1,545,784 control chromosomes in the GnomAD database, including 1,263 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 84 hom., cov: 31)

Exomes 𝑓: 0.038 ( 1179 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.857

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018931329).

BP6

Variant 1-225080404-C-A is Benign according to our data. Variant chr1-225080404-C-A is described in ClinVar as [Benign]. Clinvar id is 402646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-225080404-C-A is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1 link	c.2792C>A	p.Ala931Asp	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.2792C>A	p.Ala931Asp	missense_variant	Exon 19 of 86		NM_001367479.1	ENSP00000508305.1	A0A804HLD3
DNAH14	ENST00000430092.5 link	c.2792C>A	p.Ala931Asp	missense_variant	Exon 19 of 84	5		ENSP00000414402.1	Q0VDD8-4
DNAH14	ENST00000439375.6 link	c.2792C>A	p.Ala931Asp	missense_variant	Exon 18 of 83	5		ENSP00000392061.2	Q0VDD8-4
DNAH14	ENST00000445597.6 link	c.2594C>A	p.Ala865Asp	missense_variant	Exon 15 of 61	5		ENSP00000409472.2	Q0VDD8-1

Frequencies

GnomAD3 genomes

AF:

0.0292

AC:

4442

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00688

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.0187

Gnomad ASJ

AF:

0.0622

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0311

Gnomad FIN

AF:

0.0580

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0397

Gnomad OTH

AF:

0.0311

GnomAD3 exomes

AF:

0.0348

AC:

5274

AN:

151610

Hom.:

134

AF XY:

0.0358

AC XY:

2860

AN XY:

79908

show subpopulations

Gnomad AFR exome

AF:

0.00624

Gnomad AMR exome

AF:

0.0177

Gnomad ASJ exome

AF:

0.0615

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0360

Gnomad FIN exome

AF:

0.0630

Gnomad NFE exome

AF:

0.0398

Gnomad OTH exome

AF:

0.0383

GnomAD4 exome

AF:

0.0382

AC:

53162

AN:

1393494

Hom.:

1179

Cov.:

AF XY:

0.0383

AC XY:

26302

AN XY:

686850

show subpopulations

Gnomad4 AFR exome

AF:

0.00597

Gnomad4 AMR exome

AF:

0.0190

Gnomad4 ASJ exome

AF:

0.0616

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0362

Gnomad4 FIN exome

AF:

0.0582

Gnomad4 NFE exome

AF:

0.0395

Gnomad4 OTH exome

AF:

0.0376

GnomAD4 genome

AF:

0.0292

AC:

4443

AN:

152290

Hom.:

Cov.:

AF XY:

0.0299

AC XY:

2228

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00686

Gnomad4 AMR

AF:

0.0186

Gnomad4 ASJ

AF:

0.0622

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0313

Gnomad4 FIN

AF:

0.0580

Gnomad4 NFE

AF:

0.0397

Gnomad4 OTH

AF:

0.0312

Alfa

AF:

0.0361

Hom.:

156

Bravo

AF:

0.0260

TwinsUK

AF:

0.0450

AC:

167

ALSPAC

AF:

0.0392

AC:

151

ESP6500AA

AF:

0.00795

AC:

ESP6500EA

AF:

0.0402

AC:

128

ExAC

AF:

0.0367

AC:

918

Asia WGS

AF:

0.0110

AC:

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

0.29

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.0

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0096

T;.;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.31

T;T;.

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.038

Sift

Uncertain

0.014

D;T;T

Sift4G

Uncertain

0.042

D;T;T

Polyphen

0.22

.;B;B

Vest4

0.29

ClinPred

0.0031

GERP RS

-1.3

Varity_R

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over