Variant chr5-13901230-G-T 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.2052+22C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00957 in 1,608,384 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0099 ( 96 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0860

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=-0.85).

BP6

Variant 5-13901230-G-T is Benign according to our data. Variant chr5-13901230-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 258007.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 = 0.00643 (979/152318) while in subpopulation NFE AF= 0.0101 (687/68022). AF 95% confidence interval is 0.00947. There are 8 homozygotes in gnomad4. There are 436 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH5	NM_001369.3 linkuse as main transcript	c.2052+22C>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.2052+22C>A		intron_variant		1	NM_001369.3	ENSP00000265104	P4
DNAH5	ENST00000681290.1 linkuse as main transcript	c.2007+22C>A		intron_variant				ENSP00000505288	A1

Frequencies

GnomAD3 genomes

AF:

0.00643

AC:

979

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00972

Gnomad FIN

AF:

0.00556

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00789

AC:

1951

AN:

247340

Hom.:

AF XY:

0.00826

AC XY:

1107

AN XY:

133970

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00481

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0120

Gnomad FIN exome

AF:

0.00616

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.0105

GnomAD4 exome

AF:

0.00990

AC:

14417

AN:

1456066

Hom.:

Cov.:

AF XY:

0.00988

AC XY:

7160

AN XY:

724626

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00530

Gnomad4 ASJ exome

AF:

0.00387

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0119

Gnomad4 FIN exome

AF:

0.00656

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.00876

GnomAD4 genome

AF:

0.00643

AC:

979

AN:

152318

Hom.:

Cov.:

AF XY:

0.00585

AC XY:

436

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00973

Gnomad4 FIN

AF:

0.00556

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00783

Hom.:

Bravo

AF:

0.00625

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Primary ciliary dyskinesia 3

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.6

DANN

Benign

0.62

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