NM_001369.3:c.2578-11_2578-7delTTTTT

Variant names:

• chr5-13886135-CAAAAA-C
• rs71600031
• NM_001369.3:c.2578-11_2578-7delTTTTT

Variant summary

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

The NM_001369.3(DNAH5):​c.2578-11_2578-7delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00613 in 1,330,360 control chromosomes in the GnomAD database, including 63 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (53 hom., cov: 0)
  • Exomes 𝑓: 0.0051 (10 hom.)
• Consequence: DNAH5 NM_001369.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.52

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-CAAAAA-C is Benign according to our data. Variant chr5-13886135-CAAAAA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1283044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.2578-11_2578-7delTTTTT		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.2578-11_2578-7delTTTTT		splice_region_variant, intron_variant	Intron 17 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.2533-11_2533-7delTTTTT		splice_region_variant, intron_variant	Intron 17 of 78			ENSP00000505288.1
ENSG00000251423	ENST00000503244.2	n.254-10453_254-10449delAAAAA		intron_variant	Intron 1 of 2	4
ENSG00000251423	ENST00000637153.1	n.214-10453_214-10449delAAAAA		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 1989 AN: 123856 Hom.: 53 Cov.: 0

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00299

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0117

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0133

GnomAD3 exomes AF: 0.00998 AC: 614 AN: 61536 Hom.: 4 AF XY: 0.00914 AC XY: 287 AN XY: 31394

Gnomad AFR exome AF: 0.0608

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.00562

Gnomad EAS exome AF: 0.000607

Gnomad SAS exome AF: 0.00638

Gnomad FIN exome AF: 0.00577

Gnomad NFE exome AF: 0.00413

Gnomad OTH exome AF: 0.00811

GnomAD4 exome AF: 0.00511 AC: 6163 AN: 1206528 Hom.: 10 AF XY: 0.00476 AC XY: 2838 AN XY: 596626

Gnomad4 AFR exome AF: 0.0573

Gnomad4 AMR exome AF: 0.00918

Gnomad4 ASJ exome AF: 0.00683

Gnomad4 EAS exome AF: 0.00134

Gnomad4 SAS exome AF: 0.00319

Gnomad4 FIN exome AF: 0.00361

Gnomad4 NFE exome AF: 0.00361

Gnomad4 OTH exome AF: 0.00864

GnomAD4 genome AF: 0.0161 AC: 1995 AN: 123832 Hom.: 53 Cov.: 0 AF XY: 0.0162 AC XY: 950 AN XY: 58702

Gnomad4 AFR AF: 0.0540

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.00299

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0132

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Sep 27, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 28, 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. -

not provided Benign:1

Sep 23, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;