Variant rs7535953 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/16 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

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=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/exons	MANE	Protein	UniProt
DNAH14	NM_001367479.1 link	c.11288G>A	p.Arg3763Lys	missense_variant	71/86	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1 link	c.11288G>A	p.Arg3763Lys	missense_variant	71/86		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

GnomAD3 exomes

AF:

0.463

AC:

69057

AN:

149002

Hom.:

16279

AF XY:

0.465

AC XY:

36866

AN XY:

79214

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 SAS exome

AF:

0.550

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

Gnomad4 AFR exome

AF:

0.619

Gnomad4 AMR exome

AF:

0.485

Gnomad4 ASJ exome

AF:

0.344

Gnomad4 EAS exome

AF:

0.481

Gnomad4 SAS exome

AF:

0.544

Gnomad4 FIN exome

AF:

0.369

Gnomad4 NFE exome

AF:

0.430

Gnomad4 OTH exome

AF:

0.440

GnomAD4 genome

AF:

0.483

AC:

73375

AN:

151872

Hom.:

18352

Cov.:

AF XY:

0.478

AC XY:

35508

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.616

Gnomad4 AMR

AF:

0.464

Gnomad4 ASJ

AF:

0.338

Gnomad4 EAS

AF:

0.506

Gnomad4 SAS

AF:

0.553

Gnomad4 FIN

AF:

0.354

Gnomad4 NFE

AF:

0.428

Gnomad4 OTH

AF:

0.464

Alfa

AF:

0.435

Hom.:

28931

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

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

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

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

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