rs11958022

Variant names:

• chr5-13865945-A-C
• rs11958022
• NM_001369.3:c.4117-39T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001369.3(DNAH5):​c.4117-39T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 1,316,114 control chromosomes in the GnomAD database, including 2,940 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (1426 hom., cov: 33)
  • Exomes 𝑓: 0.033 (1514 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.428
• Publications: 2 publications found

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]

DNAH5 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000251423 (HGNC:40187):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-13865945-A-C is Benign according to our data. Variant chr5-13865945-A-C is described in ClinVar as [Benign]. Clinvar id is 258030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.4117-39T>G		intron_variant	Intron 26 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.4117-39T>G		intron_variant	Intron 26 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.4072-39T>G		intron_variant	Intron 26 of 78			ENSP00000505288.1
ENSG00000251423	ENST00000503244.2	n.253+5390A>C		intron_variant	Intron 1 of 2	4
ENSG00000251423	ENST00000637153.1	n.213+5430A>C		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13699 AN: 152146 Hom.: 1420 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0376

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.0705

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0636

GnomAD2 exomes AF: 0.0466 AC: 11419 AN: 244792 AF XY: 0.0446

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.0183

Gnomad ASJ exome AF: 0.0394

Gnomad EAS exome AF: 0.0830

Gnomad FIN exome AF: 0.0210

Gnomad NFE exome AF: 0.0219

Gnomad OTH exome AF: 0.0311

GnomAD4 exome AF: 0.0328 AC: 38138 AN: 1163850 Hom.: 1514 Cov.: 16 AF XY: 0.0330 AC XY: 19628 AN XY: 593914

African (AFR) AF: 0.255 AC: 6954 AN: 27296

American (AMR) AF: 0.0200 AC: 881 AN: 44126

Ashkenazi Jewish (ASJ) AF: 0.0380 AC: 925 AN: 24374

East Asian (EAS) AF: 0.0639 AC: 2450 AN: 38326

South Asian (SAS) AF: 0.0622 AC: 4952 AN: 79566

European-Finnish (FIN) AF: 0.0215 AC: 1118 AN: 51934

Middle Eastern (MID) AF: 0.0404 AC: 185 AN: 4578

European-Non Finnish (NFE) AF: 0.0221 AC: 18630 AN: 843142

Other (OTH) AF: 0.0404 AC: 2043 AN: 50508

GnomAD4 genome AF: 0.0902 AC: 13728 AN: 152264 Hom.: 1426 Cov.: 33 AF XY: 0.0885 AC XY: 6591 AN XY: 74460

African (AFR) AF: 0.252 AC: 10465 AN: 41510

American (AMR) AF: 0.0376 AC: 575 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3472

East Asian (EAS) AF: 0.0705 AC: 366 AN: 5192

South Asian (SAS) AF: 0.0580 AC: 280 AN: 4824

European-Finnish (FIN) AF: 0.0227 AC: 241 AN: 10620

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0219 AC: 1490 AN: 68026

Other (OTH) AF: 0.0634 AC: 134 AN: 2112

Alfa AF: 0.0393 Hom.: 237

Bravo AF: 0.0986

Asia WGS AF: 0.0720 AC: 251 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.21
DANN	Benign	0.56
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11958022; hg19: chr5-13866054;