Variant rs7527925 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.11159T>C(p.Val3720Ala) 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 1,550,514 control chromosomes in the GnomAD database, including 155,798 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 ( 18351 hom., cov: 32)

Exomes 𝑓: 0.44 ( 137447 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0710

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=1.0780426E-5).

BP6

Variant 1-225346517-T-C is Benign according to our data. Variant chr1-225346517-T-C is described in ClinVar as [Benign]. Clinvar id is 402659.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 linkuse as main transcript	c.11159T>C	p.Val3720Ala	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 linkuse as main transcript	c.11159T>C	p.Val3720Ala	missense_variant	71/86		NM_001367479.1	ENSP00000508305.1		A0A804HLD3

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73287

AN:

151852

Hom.:

18320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.507

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.395

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.461

GnomAD3 exomes

AF:

0.460

AC:

70697

AN:

153598

Hom.:

16665

AF XY:

0.463

AC XY:

37714

AN XY:

81534

show subpopulations

Gnomad AFR exome

AF:

0.627

Gnomad AMR exome

AF:

0.487

Gnomad ASJ exome

AF:

0.347

Gnomad EAS exome

AF:

0.493

Gnomad SAS exome

AF:

0.547

Gnomad FIN exome

AF:

0.363

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.428

GnomAD4 exome

AF:

0.441

AC:

616401

AN:

1398544

Hom.:

137447

Cov.:

AF XY:

0.444

AC XY:

306202

AN XY:

689822

show subpopulations

Gnomad4 AFR exome

AF:

0.620

Gnomad4 AMR exome

AF:

0.481

Gnomad4 ASJ exome

AF:

0.343

Gnomad4 EAS exome

AF:

0.481

Gnomad4 SAS exome

AF:

0.544

Gnomad4 FIN exome

AF:

0.369

Gnomad4 NFE exome

AF:

0.431

Gnomad4 OTH exome

AF:

0.441

GnomAD4 genome

AF:

0.483

AC:

73365

AN:

151970

Hom.:

18351

Cov.:

AF XY:

0.478

AC XY:

35498

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.615

Gnomad4 AMR

AF:

0.464

Gnomad4 ASJ

AF:

0.338

Gnomad4 EAS

AF:

0.506

Gnomad4 SAS

AF:

0.552

Gnomad4 FIN

AF:

0.352

Gnomad4 NFE

AF:

0.428

Gnomad4 OTH

AF:

0.464

Alfa

AF:

0.435

Hom.:

37889

Bravo

AF:

0.498

TwinsUK

AF:

0.435

AC:

1613

ALSPAC

AF:

0.435

AC:

1675

ESP6500AA

AF:

0.608

AC:

842

ESP6500EA

AF:

0.442

AC:

1404

ExAC

AF:

0.476

AC:

10017

Asia WGS

AF:

0.539

AC:

1868

AN:

3468

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

0.052

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.0020

T;.;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.086

T;T;.

MetaRNN

Benign

0.000011

T;T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.34

PROVEAN

Benign

0.54

N;N;N

REVEL

Benign

0.045

Sift

Benign

0.75

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.057

ClinPred

0.00093

GERP RS

3.5

Varity_R

0.026

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