Variant rs368185722 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001369.3(DNAH5):c.5272-32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 1,071,394 control chromosomes in the GnomAD database, including 309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 26 hom., cov: 30)

Exomes 𝑓: 0.024 ( 283 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0610

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 (BayesDel_noAF=-0.81).

BP6

Variant 5-13841936-A-G is Benign according to our data. Variant chr5-13841936-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 258043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.012 (1790/149568) while in subpopulation NFE AF= 0.0203 (1368/67404). AF 95% confidence interval is 0.0194. There are 26 homozygotes in gnomad4. There are 830 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.5272-32T>C		intron_variant		ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5 link	c.5272-32T>C		intron_variant		1	NM_001369.3	ENSP00000265104.4		Q8TE73
DNAH5	ENST00000681290.1 link	c.5227-32T>C		intron_variant				ENSP00000505288.1		A0A7P0Z455

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1792

AN:

149462

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00402

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.00613

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00375

Gnomad FIN

AF:

0.00595

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0203

Gnomad OTH

AF:

0.00538

GnomAD3 exomes

AF:

0.0203

AC:

4047

AN:

199594

Hom.:

AF XY:

0.0204

AC XY:

2235

AN XY:

109322

show subpopulations

Gnomad AFR exome

AF:

0.00821

Gnomad AMR exome

AF:

0.0114

Gnomad ASJ exome

AF:

0.0461

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00737

Gnomad FIN exome

AF:

0.00918

Gnomad NFE exome

AF:

0.0309

Gnomad OTH exome

AF:

0.0238

GnomAD4 exome

AF:

0.0236

AC:

21799

AN:

921826

Hom.:

283

Cov.:

AF XY:

0.0236

AC XY:

11301

AN XY:

478488

show subpopulations

Gnomad4 AFR exome

AF:

0.00776

Gnomad4 AMR exome

AF:

0.0151

Gnomad4 ASJ exome

AF:

0.0470

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.00851

Gnomad4 FIN exome

AF:

0.0138

Gnomad4 NFE exome

AF:

0.0273

Gnomad4 OTH exome

AF:

0.0246

GnomAD4 genome

AF:

0.0120

AC:

1790

AN:

149568

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

830

AN XY:

73082

show subpopulations

Gnomad4 AFR

AF:

0.00401

Gnomad4 AMR

AF:

0.0100

Gnomad4 ASJ

AF:

0.00613

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00355

Gnomad4 FIN

AF:

0.00595

Gnomad4 NFE

AF:

0.0203

Gnomad4 OTH

AF:

0.00532

Alfa

AF:

0.0211

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 17, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

DNAH5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 07, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.6

DANN

Benign

0.60

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