5-13865871-T-C

Variant names:

• chr5-13865871-T-C
• rs7703349
• NM_001369.3:c.4152A>G

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.4152A>G​(p.Thr1384Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,606,262 control chromosomes in the GnomAD database, including 178,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1384T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.49 (18244 hom., cov: 32)
  • Exomes 𝑓: 0.47 (160018 hom.)
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.0420
• Publications: 18 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=-0.56).
• BP6: Variant 5-13865871-T-C is Benign according to our data. Variant chr5-13865871-T-C is described in ClinVar as Benign. ClinVar VariationId is 178751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.042 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 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.4152A>G	p.Thr1384Thr	synonymous	Exon 27 of 79	NP_001360.1	Q8TE73
	DNAH5-AS1	NR_199035.1		n.117+5316T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.4152A>G	p.Thr1384Thr	synonymous	Exon 27 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.4107A>G	p.Thr1369Thr	synonymous	Exon 27 of 79	ENSP00000505288.1	A0A7P0Z455
	DNAH5-AS1	ENST00000503244.2	TSL:4	n.253+5316T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73749 AN: 151872 Hom.: 18216 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.465

GnomAD2 exomes AF: 0.449 AC: 112264 AN: 249798 AF XY: 0.455

Gnomad AFR exome AF: 0.572

Gnomad AMR exome AF: 0.312

Gnomad ASJ exome AF: 0.398

Gnomad EAS exome AF: 0.322

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.467

Gnomad OTH exome AF: 0.430

GnomAD4 exome AF: 0.465 AC: 676687 AN: 1454272 Hom.: 160018 Cov.: 33 AF XY: 0.467 AC XY: 337688 AN XY: 723858

African (AFR) AF: 0.580 AC: 19343 AN: 33324

American (AMR) AF: 0.321 AC: 14364 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 10346 AN: 26104

East Asian (EAS) AF: 0.324 AC: 12833 AN: 39640

South Asian (SAS) AF: 0.530 AC: 45619 AN: 86020

European-Finnish (FIN) AF: 0.499 AC: 26645 AN: 53356

Middle Eastern (MID) AF: 0.389 AC: 2223 AN: 5722

European-Non Finnish (NFE) AF: 0.469 AC: 517861 AN: 1105266

Other (OTH) AF: 0.456 AC: 27453 AN: 60152

GnomAD4 genome AF: 0.486 AC: 73840 AN: 151990 Hom.: 18244 Cov.: 32 AF XY: 0.483 AC XY: 35885 AN XY: 74316

African (AFR) AF: 0.569 AC: 23582 AN: 41440

American (AMR) AF: 0.379 AC: 5787 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1363 AN: 3464

East Asian (EAS) AF: 0.332 AC: 1717 AN: 5174

South Asian (SAS) AF: 0.524 AC: 2522 AN: 4816

European-Finnish (FIN) AF: 0.508 AC: 5363 AN: 10560

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32069 AN: 67946

Other (OTH) AF: 0.468 AC: 989 AN: 2112

Alfa AF: 0.468 Hom.: 63274

Bravo AF: 0.474

Asia WGS AF: 0.455 AC: 1584 AN: 3476

EpiCase AF: 0.454

EpiControl AF: 0.452

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-0.042
Mutation Taster		=92/8	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: rs7703349; hg19: chr5-13865980; COSMIC: COSV54212563;