5-13886135-CAAAAAAAAAA-CAAAAAAAAAAA

Variant names:

• chr5-13886135-C-CA
• rs71600031
• NM_001369.3:c.2578-7dupT

Variant summary

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

The NM_001369.3(DNAH5):​c.2578-7dupT 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 0.021 (65 hom., cov: 0)
  • Exomes 𝑓: 0.019 (8 hom.)
• Consequence: DNAH5 NM_001369.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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:40187):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 5-13886135-C-CA is Benign according to our data. Variant chr5-13886135-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 1269037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.2578-7dupT		splice_region_variant, intron_variant	Intron 17 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.2578-7_2578-6insT		splice_region_variant, intron_variant	Intron 17 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.2533-7_2533-6insT		splice_region_variant, intron_variant	Intron 17 of 78			ENSP00000505288.1
ENSG00000251423	ENST00000503244.2	n.254-10454_254-10453insA		intron_variant	Intron 1 of 2	4
ENSG00000251423	ENST00000637153.1	n.214-10454_214-10453insA		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 2583 AN: 123802 Hom.: 65 Cov.: 0

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00532

Gnomad EAS AF: 0.0109

Gnomad SAS AF: 0.0165

Gnomad FIN AF: 0.000835

Gnomad MID AF: 0.0273

Gnomad NFE AF: 0.00311

Gnomad OTH AF: 0.0218

GnomAD3 exomes AF: 0.0376 AC: 2316 AN: 61536 Hom.: 8 AF XY: 0.0361 AC XY: 1132 AN XY: 31394

Gnomad AFR exome AF: 0.0531

Gnomad AMR exome AF: 0.0362

Gnomad ASJ exome AF: 0.0308

Gnomad EAS exome AF: 0.0975

Gnomad SAS exome AF: 0.0225

Gnomad FIN exome AF: 0.0183

Gnomad NFE exome AF: 0.0312

Gnomad OTH exome AF: 0.0319

GnomAD4 exome AF: 0.0188 AC: 22720 AN: 1205682 Hom.: 8 Cov.: 0 AF XY: 0.0188 AC XY: 11187 AN XY: 595948

Gnomad4 AFR exome AF: 0.0428

Gnomad4 AMR exome AF: 0.0253

Gnomad4 ASJ exome AF: 0.0222

Gnomad4 EAS exome AF: 0.0436

Gnomad4 SAS exome AF: 0.0240

Gnomad4 FIN exome AF: 0.0162

Gnomad4 NFE exome AF: 0.0166

Gnomad4 OTH exome AF: 0.0221

GnomAD4 genome AF: 0.0209 AC: 2583 AN: 123780 Hom.: 65 Cov.: 0 AF XY: 0.0206 AC XY: 1211 AN XY: 58676

Gnomad4 AFR AF: 0.0624

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.00532

Gnomad4 EAS AF: 0.0109

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.000835

Gnomad4 NFE AF: 0.00311

Gnomad4 OTH AF: 0.0217

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Aug 07, 2015

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Sep 27, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:1

Aug 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs71600031; hg19: chr5-13886244;