rs1303708125

Positions:

• chr5-13886135-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001369.3(DNAH5):​c.2578-6G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,217,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 18)
  • Exomes 𝑓: 0.0012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAH5 NM_001369.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001886
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-13886135-C-A is Benign according to our data. Variant chr5-13886135-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 454759.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-13886135-C-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.2578-6G>T		splice_region_variant, splice_polypyrimidine_tract_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.2578-6G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001369.3	ENSP00000265104	P4
	ENST00000503244.2	n.254-10454C>A		intron_variant, non_coding_transcript_variant		4
DNAH5	ENST00000681290.1	c.2533-6G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant				ENSP00000505288	A1
	ENST00000637153.1	n.214-10454C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 214 AN: 123602 Hom.: 0 Cov.: 18 FAILED QC

Gnomad AFR AF: 0.00139

Gnomad AMI AF: 0.00369

Gnomad AMR AF: 0.00175

Gnomad ASJ AF: 0.000999

Gnomad EAS AF: 0.00420

Gnomad SAS AF: 0.000775

Gnomad FIN AF: 0.00100

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00189

Gnomad OTH AF: 0.00302

GnomAD4 exome AF: 0.00123 AC: 1495 AN: 1217844 Hom.: 0 Cov.: 24 AF XY: 0.00134 AC XY: 807 AN XY: 602144

Gnomad4 AFR exome AF: 0.000822

Gnomad4 AMR exome AF: 0.00256

Gnomad4 ASJ exome AF: 0.00235

Gnomad4 EAS exome AF: 0.00273

Gnomad4 SAS exome AF: 0.00325

Gnomad4 FIN exome AF: 0.00191

Gnomad4 NFE exome AF: 0.000953

Gnomad4 OTH exome AF: 0.00140

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00174 AC: 215 AN: 123580 Hom.: 0 Cov.: 18 AF XY: 0.00162 AC XY: 95 AN XY: 58606

Gnomad4 AFR AF: 0.00139

Gnomad4 AMR AF: 0.00175

Gnomad4 ASJ AF: 0.000999

Gnomad4 EAS AF: 0.00421

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00100

Gnomad4 NFE AF: 0.00189

Gnomad4 OTH AF: 0.00301

Alfa AF: 0.00228 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.13
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.0080
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: rs1303708125; hg19: chr5-13886244;