Variant 1-225079264-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001367479.1(DNAH14):c.2482C>G(p.Leu828Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,547,610 control chromosomes in the GnomAD database, including 662,157 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 0.80 ( 51748 hom., cov: 31)

Exomes 𝑓: 0.93 ( 610409 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.359

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.739373E-7).

BP6

Variant 1-225079264-C-G is Benign according to our data. Variant chr1-225079264-C-G is described in ClinVar as [Benign]. Clinvar id is 402645.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH14	NM_001367479.1 linkuse as main transcript	c.2482C>G	p.Leu828Val	missense_variant	18/86	ENST00000682510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH14	ENST00000682510.1 linkuse as main transcript	c.2482C>G	p.Leu828Val	missense_variant	18/86		NM_001367479.1	P1
DNAH14	ENST00000430092.5 linkuse as main transcript	c.2482C>G	p.Leu828Val	missense_variant	18/84	5			Q0VDD8-4
DNAH14	ENST00000439375.6 linkuse as main transcript	c.2482C>G	p.Leu828Val	missense_variant	17/83	5			Q0VDD8-4
DNAH14	ENST00000445597.6 linkuse as main transcript	c.2284C>G	p.Leu762Val	missense_variant	14/61	5			Q0VDD8-1

Frequencies

GnomAD3 genomes

AF:

0.798

AC:

121258

AN:

151968

Hom.:

51730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.474

Gnomad AMI

AF:

0.980

Gnomad AMR

AF:

0.796

Gnomad ASJ

AF:

0.916

Gnomad EAS

AF:

0.711

Gnomad SAS

AF:

0.850

Gnomad FIN

AF:

0.967

Gnomad MID

AF:

0.845

Gnomad NFE

AF:

0.962

Gnomad OTH

AF:

0.823

GnomAD3 exomes

AF:

0.870

AC:

133093

AN:

153012

Hom.:

59222

AF XY:

0.879

AC XY:

71214

AN XY:

81030

show subpopulations

Gnomad AFR exome

AF:

0.472

Gnomad AMR exome

AF:

0.758

Gnomad ASJ exome

AF:

0.927

Gnomad EAS exome

AF:

0.701

Gnomad SAS exome

AF:

0.867

Gnomad FIN exome

AF:

0.969

Gnomad NFE exome

AF:

0.960

Gnomad OTH exome

AF:

0.889

GnomAD4 exome

AF:

0.931

AC:

1298699

AN:

1395524

Hom.:

610409

Cov.:

AF XY:

0.931

AC XY:

640552

AN XY:

688178

show subpopulations

Gnomad4 AFR exome

AF:

0.454

Gnomad4 AMR exome

AF:

0.766

Gnomad4 ASJ exome

AF:

0.925

Gnomad4 EAS exome

AF:

0.724

Gnomad4 SAS exome

AF:

0.869

Gnomad4 FIN exome

AF:

0.968

Gnomad4 NFE exome

AF:

0.961

Gnomad4 OTH exome

AF:

0.894

GnomAD4 genome

AF:

0.798

AC:

121312

AN:

152086

Hom.:

51748

Cov.:

AF XY:

0.798

AC XY:

59301

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.473

Gnomad4 AMR

AF:

0.796

Gnomad4 ASJ

AF:

0.916

Gnomad4 EAS

AF:

0.712

Gnomad4 SAS

AF:

0.852

Gnomad4 FIN

AF:

0.967

Gnomad4 NFE

AF:

0.962

Gnomad4 OTH

AF:

0.823

Alfa

AF:

0.921

Hom.:

17111

Bravo

AF:

0.769

TwinsUK

AF:

0.960

AC:

3560

ALSPAC

AF:

0.955

AC:

3679

ESP6500AA

AF:

0.519

AC:

718

ESP6500EA

AF:

0.961

AC:

3053

ExAC

AF:

0.860

AC:

19727

Asia WGS

AF:

0.753

AC:

2618

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.067

DEOGEN2

Benign

0.0011

T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.27

T;T;.

MetaRNN

Benign

5.7e-7

T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.44

PROVEAN

Benign

1.5

N;N;N

REVEL

Benign

0.027

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.043

ClinPred

0.0035

GERP RS

2.4

Varity_R

0.044

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