rs6554817

Positions:

• chr5-13820547-G-A
• chr5-13820547-G-T

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.6688-48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,604,744 control chromosomes in the GnomAD database, including 36,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3387 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33466 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.60

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=-0.98).
• BP6: Variant 5-13820547-G-A is Benign according to our data. Variant chr5-13820547-G-A is described in ClinVar as [Benign]. Clinvar id is 258054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.6688-48C>T		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.6688-48C>T		intron_variant		1	NM_001369.3	P4
DNAH5	ENST00000681290.1	c.6643-48C>T		intron_variant				A1
DNAH5	ENST00000683090.1	n.1619-48C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31017 AN: 151976 Hom.: 3389 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.207

GnomAD3 exomes AF: 0.213 AC: 52560 AN: 246692 Hom.: 6686 AF XY: 0.210 AC XY: 28081 AN XY: 133794

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.160

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.540

Gnomad SAS exome AF: 0.164

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.207 AC: 301275 AN: 1452652 Hom.: 33466 Cov.: 30 AF XY: 0.206 AC XY: 148915 AN XY: 723160

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.487

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.204 AC: 31028 AN: 152092 Hom.: 3387 Cov.: 32 AF XY: 0.202 AC XY: 15044 AN XY: 74332

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.206

Alfa AF: 0.198 Hom.: 566

Bravo AF: 0.207

Asia WGS AF: 0.303 AC: 1051 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.35
DANN	Benign	0.60

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: rs6554817; hg19: chr5-13820656;