chr5-13811780-C-T

Position:

chr5-13811780-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001369.3(DNAH5):c.7274G>A(p.Arg2425His) variant causes a missense change. The variant allele was found at a frequency of 0.0044 in 1,614,062 control chromosomes in the GnomAD database, including 210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 99 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 111 hom. )

Consequence

DNAH5
NM_001369.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 3.98

Variant links:

Genes affected

DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

DNAH5 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=0.002856791).

BP6

Variant 5-13811780-C-T is Benign according to our data. Variant chr5-13811780-C-T is described in ClinVar as [Benign]. Clinvar id is 226606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13811780-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH5	NM_001369.3 linkuse as main transcript	c.7274G>A	p.Arg2425His	missense_variant	44/79	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5 linkuse as main transcript	c.7274G>A	p.Arg2425His	missense_variant	44/79	1	NM_001369.3	ENSP00000265104	P4
DNAH5	ENST00000681290.1 linkuse as main transcript	c.7229G>A	p.Arg2410His	missense_variant	44/79			ENSP00000505288	A1

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

3276

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0720

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.00642

AC:

1613

AN:

251414

Hom.:

AF XY:

0.00500

AC XY:

680

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0773

Gnomad AMR exome

AF:

0.00656

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000703

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00261

AC:

3815

AN:

1461856

Hom.:

111

Cov.:

AF XY:

0.00228

AC XY:

1656

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0748

Gnomad4 AMR exome

AF:

0.00720

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000437

Gnomad4 OTH exome

AF:

0.00594

GnomAD4 genome

AF:

0.0216

AC:

3282

AN:

152206

Hom.:

Cov.:

AF XY:

0.0207

AC XY:

1543

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0719

Gnomad4 AMR

AF:

0.0135

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.00426

Hom.:

Bravo

AF:

0.0252

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0731

AC:

322

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00752

AC:

913

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:3

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Dec 24, 2014	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Arg2425His in exon 44 of DNAH5: This variant is not expected to have clinical si gnificance because it has been identified in 7.3% (322/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs35900306). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 31, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary ciliary dyskinesia 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 21, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.092

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.86

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.0

REVEL

Benign

0.14

Sift

Benign

0.51

Polyphen

0.13

Vest4

0.36

MVP

0.54

MPC

0.12

ClinPred

0.033

GERP RS

5.8

Varity_R

0.15

gMVP

0.58

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