5-13886135-CAAAAAAAAAA-CAAAAAAAAA

Position:

• chr5-13886135-CAAAAAAAAAA-CAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001369.3(DNAH5):​c.2578-7delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (817 hom., cov: 0)
  • Exomes 𝑓: 0.14 (142 hom.)
• Consequence: DNAH5 NM_001369.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0110

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]

ENSG00000251423 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 5-13886135-CA-C is Benign according to our data. Variant chr5-13886135-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 414363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13886135-CA-C is described in Lovd as [Benign]. Variant chr5-13886135-CA-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.2578-7delT		splice_region_variant, intron_variant		ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.2578-7delT		splice_region_variant, intron_variant		1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.2533-7delT		splice_region_variant, intron_variant				ENSP00000505288.1
ENSG00000251423	ENST00000503244.2	n.254-10435delA		intron_variant		4
ENSG00000251423	ENST00000637153.1	n.214-10435delA		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.123 AC: 15189 AN: 123680 Hom.: 818 Cov.: 0

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.0591

Gnomad AMR AF: 0.0813

Gnomad ASJ AF: 0.0698

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.0827

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.102

GnomAD3 exomes AF: 0.102 AC: 6270 AN: 61536 Hom.: 3 AF XY: 0.0994 AC XY: 3119 AN XY: 31394

Gnomad AFR exome AF: 0.0968

Gnomad AMR exome AF: 0.0795

Gnomad ASJ exome AF: 0.0896

Gnomad EAS exome AF: 0.168

Gnomad SAS exome AF: 0.0761

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.145 AC: 170185 AN: 1175852 Hom.: 142 Cov.: 0 AF XY: 0.142 AC XY: 82622 AN XY: 580464

Gnomad4 AFR exome AF: 0.0974

Gnomad4 AMR exome AF: 0.0729

Gnomad4 ASJ exome AF: 0.0970

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.0881

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.123 AC: 15190 AN: 123658 Hom.: 817 Cov.: 0 AF XY: 0.121 AC XY: 7092 AN XY: 58598

Gnomad4 AFR AF: 0.0795

Gnomad4 AMR AF: 0.0813

Gnomad4 ASJ AF: 0.0698

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.0767

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.103

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 02, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Primary ciliary dyskinesia Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Aug 05, 2015	This alteration is classified as likely 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. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs71600031; hg19: chr5-13886244;