chr5-13900236-A-G

Variant names:

• chr5-13900236-A-G
• rs1445823
• NM_001369.3:c.2229T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001369.3(DNAH5):​c.2229T>C​(p.Asp743Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,613,110 control chromosomes in the GnomAD database, including 186,553 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (22023 hom., cov: 32)
  • Exomes 𝑓: 0.47 (164530 hom.)
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.0730
• Publications: 23 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAH5-AS1 (HGNC:40187):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-13900236-A-G is Benign according to our data. Variant chr5-13900236-A-G is described in ClinVar as Benign. ClinVar VariationId is 178755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.073 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.2229T>C	p.Asp743Asp	synonymous	Exon 15 of 79	NP_001360.1	Q8TE73
	DNAH5-AS1	NR_199035.1		n.2976A>G		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.2229T>C	p.Asp743Asp	synonymous	Exon 15 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.2184T>C	p.Asp728Asp	synonymous	Exon 15 of 79	ENSP00000505288.1	A0A7P0Z455
	DNAH5-AS1	ENST00000503244.2	TSL:4	n.3112A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.526 AC: 80009 AN: 151980 Hom.: 22013 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.503

GnomAD2 exomes AF: 0.500 AC: 125510 AN: 251038 AF XY: 0.492

Gnomad AFR exome AF: 0.665

Gnomad AMR exome AF: 0.471

Gnomad ASJ exome AF: 0.487

Gnomad EAS exome AF: 0.891

Gnomad FIN exome AF: 0.428

Gnomad NFE exome AF: 0.453

Gnomad OTH exome AF: 0.493

GnomAD4 exome AF: 0.467 AC: 682703 AN: 1461012 Hom.: 164530 Cov.: 42 AF XY: 0.466 AC XY: 338470 AN XY: 726852

African (AFR) AF: 0.666 AC: 22298 AN: 33478

American (AMR) AF: 0.476 AC: 21266 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 12622 AN: 26122

East Asian (EAS) AF: 0.869 AC: 34490 AN: 39694

South Asian (SAS) AF: 0.442 AC: 38076 AN: 86224

European-Finnish (FIN) AF: 0.437 AC: 23367 AN: 53412

Middle Eastern (MID) AF: 0.526 AC: 3030 AN: 5764

European-Non Finnish (NFE) AF: 0.448 AC: 497978 AN: 1111242

Other (OTH) AF: 0.490 AC: 29576 AN: 60360

GnomAD4 genome AF: 0.526 AC: 80072 AN: 152098 Hom.: 22023 Cov.: 32 AF XY: 0.524 AC XY: 38992 AN XY: 74356

African (AFR) AF: 0.661 AC: 27430 AN: 41468

American (AMR) AF: 0.479 AC: 7324 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1660 AN: 3472

East Asian (EAS) AF: 0.876 AC: 4548 AN: 5190

South Asian (SAS) AF: 0.452 AC: 2179 AN: 4818

European-Finnish (FIN) AF: 0.424 AC: 4476 AN: 10562

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30866 AN: 67974

Other (OTH) AF: 0.501 AC: 1060 AN: 2116

Alfa AF: 0.470 Hom.: 36484

Bravo AF: 0.538

Asia WGS AF: 0.634 AC: 2200 AN: 3478

EpiCase AF: 0.457

EpiControl AF: 0.452

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Primary ciliary dyskinesia (3)
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia 3 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.4
DANN	Benign	0.61
PhyloP100		0.073
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1445823; hg19: chr5-13900345; COSMIC: COSV54256012; COSMIC: COSV54256012;