Variant rs150679902 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.1537-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 1,399,426 control chromosomes in the GnomAD database, including 427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 30 hom., cov: 32)

Exomes 𝑓: 0.024 ( 397 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.148

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=-0.84).

BP6

Variant 5-13911543-C-T is Benign according to our data. Variant chr5-13911543-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258003.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 = 0.017 (2584/152072) while in subpopulation NFE AF= 0.0266 (1811/67980). AF 95% confidence interval is 0.0256. There are 30 homozygotes in gnomad4. There are 1196 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH5	NM_001369.3 linkuse as main transcript	c.1537-50G>A		intron_variant		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.1537-50G>A		intron_variant		1	NM_001369.3	ENSP00000265104	P4

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2585

AN:

151954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00539

Gnomad AMI

AF:

0.0451

Gnomad AMR

AF:

0.0142

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00664

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0266

Gnomad OTH

AF:

0.0211

GnomAD3 exomes

AF:

0.0166

AC:

3696

AN:

222856

Hom.:

AF XY:

0.0171

AC XY:

2079

AN XY:

121792

show subpopulations

Gnomad AFR exome

AF:

0.00482

Gnomad AMR exome

AF:

0.00910

Gnomad ASJ exome

AF:

0.0255

Gnomad EAS exome

AF:

0.0000668

Gnomad SAS exome

AF:

0.00764

Gnomad FIN exome

AF:

0.0138

Gnomad NFE exome

AF:

0.0253

Gnomad OTH exome

AF:

0.0171

GnomAD4 exome

AF:

0.0237

AC:

29515

AN:

1247354

Hom.:

397

Cov.:

AF XY:

0.0234

AC XY:

14745

AN XY:

630836

show subpopulations

Gnomad4 AFR exome

AF:

0.00456

Gnomad4 AMR exome

AF:

0.00917

Gnomad4 ASJ exome

AF:

0.0213

Gnomad4 EAS exome

AF:

0.0000558

Gnomad4 SAS exome

AF:

0.00729

Gnomad4 FIN exome

AF:

0.0160

Gnomad4 NFE exome

AF:

0.0279

Gnomad4 OTH exome

AF:

0.0220

GnomAD4 genome

AF:

0.0170

AC:

2584

AN:

152072

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1196

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00537

Gnomad4 AMR

AF:

0.0142

Gnomad4 ASJ

AF:

0.0245

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00643

Gnomad4 FIN

AF:

0.0120

Gnomad4 NFE

AF:

0.0266

Gnomad4 OTH

AF:

0.0209

Alfa

AF:

0.0201

Hom.:

Bravo

AF:

0.0166

Asia WGS

AF:

0.00404

AC:

AN:

3476

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	Feb 11, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.37

DANN

Benign

0.17

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