Variant chr1-225318592-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.9250A>G(p.Asn3084Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 1,544,522 control chromosomes in the GnomAD database, including 7,772 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1181 hom., cov: 32)

Exomes 𝑓: 0.084 ( 6591 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.879

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=0.0031424463).

BP6

Variant 1-225318592-A-G is Benign according to our data. Variant chr1-225318592-A-G is described in ClinVar as [Benign]. Clinvar id is 402655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 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.9250A>G	p.Asn3084Asp	missense_variant	61/86	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.9250A>G	p.Asn3084Asp	missense_variant	61/86		NM_001367479.1	ENSP00000508305	P1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17207

AN:

152114

Hom.:

1177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.0487

Gnomad EAS

AF:

0.266

Gnomad SAS

AF:

0.0897

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0745

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.119

AC:

18148

AN:

152648

Hom.:

1547

AF XY:

0.111

AC XY:

8963

AN XY:

80572

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.227

Gnomad ASJ exome

AF:

0.0468

Gnomad EAS exome

AF:

0.277

Gnomad SAS exome

AF:

0.0757

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.0707

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0844

AC:

117578

AN:

1392288

Hom.:

6591

Cov.:

AF XY:

0.0837

AC XY:

57447

AN XY:

686304

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.214

Gnomad4 ASJ exome

AF:

0.0479

Gnomad4 EAS exome

AF:

0.291

Gnomad4 SAS exome

AF:

0.0740

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.0708

Gnomad4 OTH exome

AF:

0.0923

GnomAD4 genome

AF:

0.113

AC:

17230

AN:

152234

Hom.:

1181

Cov.:

AF XY:

0.119

AC XY:

8821

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.166

Gnomad4 ASJ

AF:

0.0487

Gnomad4 EAS

AF:

0.266

Gnomad4 SAS

AF:

0.0879

Gnomad4 FIN

AF:

0.138

Gnomad4 NFE

AF:

0.0745

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.0767

Hom.:

856

Bravo

AF:

0.117

TwinsUK

AF:

0.0704

AC:

261

ALSPAC

AF:

0.0675

AC:

260

ESP6500AA

AF:

0.153

AC:

212

ESP6500EA

AF:

0.0669

AC:

213

ExAC

AF:

0.0849

AC:

2113

Asia WGS

AF:

0.170

AC:

589

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

0.079

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

T;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.45

T;T;.

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.80

N;N;N

REVEL

Benign

0.0070

Sift

Benign

0.52

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.038

.;B;B

Vest4

0.15

ClinPred

0.0032

GERP RS

1.5

Varity_R

0.057

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