rs112344370

chr5-13814859-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001369.3(DNAH5):c.6989-13T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,611,918 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (66 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (65 hom.)
• Consequence: DNAH5 NM_001369.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0190

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-13814859-A-G is Benign according to our data. Variant chr5-13814859-A-G is described in ClinVar as [Benign]. Clinvar id is 178747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13814859-A-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0147 (2236/151824) while in subpopulation AFR AF= 0.0513 (2120/41358). AF 95% confidence interval is 0.0494. There are 66 homozygotes in gnomad4. There are 1039 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 63 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.6989-13T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.6989-13T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001369.3	P4
DNAH5	ENST00000681290.1	c.6944-13T>C		splice_polypyrimidine_tract_variant, intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2222 AN: 151708 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00506

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000418

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00379 AC: 941 AN: 248200 Hom.: 29 AF XY: 0.00281 AC XY: 379 AN XY: 134650

Gnomad AFR exome AF: 0.0530

Gnomad AMR exome AF: 0.00247

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000986

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000116

Gnomad OTH exome AF: 0.000992

GnomAD4 exome AF: 0.00144 AC: 2107 AN: 1460094 Hom.: 65 Cov.: 33 AF XY: 0.00128 AC XY: 930 AN XY: 726300

Gnomad4 AFR exome AF: 0.0513

Gnomad4 AMR exome AF: 0.00253

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000342

Gnomad4 OTH exome AF: 0.00346

GnomAD4 genome AF: 0.0147 AC: 2236 AN: 151824 Hom.: 66 Cov.: 32 AF XY: 0.0140 AC XY: 1039 AN XY: 74220

Gnomad4 AFR AF: 0.0513

Gnomad4 AMR AF: 0.00505

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00752 Hom.: 9

Bravo AF: 0.0170

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	6989-13T>C in intron 42 of DNAH5: This variant is not expected to have clinical significance because it has been identified in 4.8% (211/4406) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs112344370). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2019

- -

Primary ciliary dyskinesia 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.7
Dann	Benign	0.73

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

Other links and lift over

dbSNP: rs112344370; hg19: chr5-13814968;