rs4701988

Variant names:

• chr5-13850630-T-A
• rs4701988
• NM_001369.3:c.5114+22A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-13850630-T-A
• chr5-13850630-T-C
• chr5-13850630-T-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.5114+22A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,608,968 control chromosomes in the GnomAD database, including 122,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9747 hom., cov: 33)
  • Exomes 𝑓: 0.39 (112821 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.858
• Publications: 5 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-13850630-T-A is Benign according to our data. Variant chr5-13850630-T-A is described in ClinVar as Benign. ClinVar VariationId is 258038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.5114+22A>T		intron_variant	Intron 31 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.5114+22A>T		intron_variant	Intron 31 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.5069+22A>T		intron_variant	Intron 31 of 78			ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52752 AN: 152028 Hom.: 9750 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.387

GnomAD2 exomes AF: 0.388 AC: 97255 AN: 250900 AF XY: 0.388

Gnomad AFR exome AF: 0.206

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.479

Gnomad EAS exome AF: 0.595

Gnomad FIN exome AF: 0.342

Gnomad NFE exome AF: 0.396

Gnomad OTH exome AF: 0.422

GnomAD4 exome AF: 0.389 AC: 566610 AN: 1456822 Hom.: 112821 Cov.: 30 AF XY: 0.388 AC XY: 281191 AN XY: 725124

African (AFR) AF: 0.200 AC: 6673 AN: 33394

American (AMR) AF: 0.401 AC: 17944 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 12491 AN: 26100

East Asian (EAS) AF: 0.584 AC: 23141 AN: 39654

South Asian (SAS) AF: 0.310 AC: 26729 AN: 86120

European-Finnish (FIN) AF: 0.348 AC: 18572 AN: 53392

Middle Eastern (MID) AF: 0.443 AC: 2457 AN: 5548

European-Non Finnish (NFE) AF: 0.392 AC: 434678 AN: 1107700

Other (OTH) AF: 0.397 AC: 23925 AN: 60214

GnomAD4 genome AF: 0.347 AC: 52753 AN: 152146 Hom.: 9747 Cov.: 33 AF XY: 0.349 AC XY: 25938 AN XY: 74362

African (AFR) AF: 0.210 AC: 8734 AN: 41516

American (AMR) AF: 0.406 AC: 6207 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1678 AN: 3468

East Asian (EAS) AF: 0.580 AC: 2996 AN: 5166

South Asian (SAS) AF: 0.317 AC: 1526 AN: 4810

European-Finnish (FIN) AF: 0.336 AC: 3555 AN: 10596

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26703 AN: 67990

Other (OTH) AF: 0.386 AC: 815 AN: 2112

Alfa AF: 0.292 Hom.: 1204

Bravo AF: 0.352

Asia WGS AF: 0.410 AC: 1426 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 04, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 3 Benign:1

Jun 15, 2021

Pars Genome Lab

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	-0.78
CADD	Benign	8.8
DANN	Benign	0.75
PhyloP100		0.86
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: rs4701988; hg19: chr5-13850739; COSMIC: COSV54208540;