Variant 1-225345982-A-G 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.10699A>G(p.Lys3567Glu) 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 1,548,984 control chromosomes in the GnomAD database, including 155,635 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18359 hom., cov: 32)

Exomes 𝑓: 0.44 ( 137276 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.23

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=1.5726708E-5).

BP6

Variant 1-225345982-A-G is Benign according to our data. Variant chr1-225345982-A-G is described in ClinVar as [Benign]. Clinvar id is 402657.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.10699A>G	p.Lys3567Glu	missense_variant	70/86	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.10699A>G	p.Lys3567Glu	missense_variant	70/86		NM_001367479.1	ENSP00000508305	P1

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73321

AN:

151914

Hom.:

18328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.506

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.461

GnomAD3 exomes

AF:

0.460

AC:

70904

AN:

154222

Hom.:

16694

AF XY:

0.462

AC XY:

37853

AN XY:

81908

show subpopulations

Gnomad AFR exome

AF:

0.627

Gnomad AMR exome

AF:

0.488

Gnomad ASJ exome

AF:

0.346

Gnomad EAS exome

AF:

0.494

Gnomad SAS exome

AF:

0.547

Gnomad FIN exome

AF:

0.364

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.429

GnomAD4 exome

AF:

0.441

AC:

615626

AN:

1396952

Hom.:

137276

Cov.:

AF XY:

0.444

AC XY:

305882

AN XY:

689126

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:

73399

AN:

152032

Hom.:

18359

Cov.:

AF XY:

0.478

AC XY:

35513

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.615

Gnomad4 AMR

AF:

0.464

Gnomad4 ASJ

AF:

0.338

Gnomad4 EAS

AF:

0.505

Gnomad4 SAS

AF:

0.552

Gnomad4 FIN

AF:

0.352

Gnomad4 NFE

AF:

0.428

Gnomad4 OTH

AF:

0.464

Alfa

AF:

0.436

Hom.:

36754

Bravo

AF:

0.498

TwinsUK

AF:

0.435

AC:

1612

ALSPAC

AF:

0.434

AC:

1674

ESP6500AA

AF:

0.608

AC:

842

ESP6500EA

AF:

0.442

AC:

1406

ExAC

AF:

0.465

AC:

10706

Asia WGS

AF:

0.540

AC:

1875

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

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

0.059

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.13

DEOGEN2

Benign

0.0021

T;.;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.37

T;T;.

MetaRNN

Benign

0.000016

T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.44

PROVEAN

Benign

2.3

N;N;N

REVEL

Benign

0.071

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.031

ClinPred

0.0013

GERP RS

3.4

Varity_R

0.054

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