rs6554813

chr5-13762930-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001369.3(DNAH5):c.10102-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,587,034 control chromosomes in the GnomAD database, including 66,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7641 hom., cov: 33)
  • Exomes 𝑓: 0.28 (58997 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.327

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=-0.85).
• BP6: Variant 5-13762930-G-A is Benign according to our data. Variant chr5-13762930-G-A is described in ClinVar as [Benign]. Clinvar id is 257971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.10102-29C>T		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.10102-29C>T		intron_variant		1	NM_001369.3	P4
DNAH5	ENST00000681290.1	c.10057-29C>T		intron_variant				A1
DNAH5	ENST00000504001.3	n.610-29C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46581 AN: 151932 Hom.: 7624 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.280

GnomAD3 exomes AF: 0.297 AC: 73526 AN: 247876 Hom.: 11931 AF XY: 0.301 AC XY: 40360 AN XY: 134234

Gnomad AFR exome AF: 0.361

Gnomad AMR exome AF: 0.297

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.0929

Gnomad SAS exome AF: 0.439

Gnomad FIN exome AF: 0.422

Gnomad NFE exome AF: 0.268

Gnomad OTH exome AF: 0.267

GnomAD4 exome AF: 0.279 AC: 400613 AN: 1434982 Hom.: 58997 Cov.: 28 AF XY: 0.284 AC XY: 203151 AN XY: 715752

Gnomad4 AFR exome AF: 0.360

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.307 AC: 46649 AN: 152052 Hom.: 7641 Cov.: 33 AF XY: 0.314 AC XY: 23308 AN XY: 74316

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.283

Alfa AF: 0.294 Hom.: 1616

Bravo AF: 0.290

Asia WGS AF: 0.324 AC: 1124 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 3 Benign:2

Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	9.6
Dann	Benign	0.72

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: rs6554813; hg19: chr5-13763039;