rs11958721

Variant names:

• chr5-13866175-A-G
• rs11958721
• NM_001369.3:c.4116+45T>C

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.4116+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 1,575,336 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (116 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (98 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.470
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-13866175-A-G is Benign according to our data. Variant chr5-13866175-A-G is described in ClinVar as Benign. ClinVar VariationId is 258029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0671 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.4116+45T>C		intron	N/A	NP_001360.1	Q8TE73
	DNAH5-AS1	NR_199035.1		n.117+5620A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.4116+45T>C		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.4071+45T>C		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5-AS1	ENST00000503244.2	TSL:4	n.253+5620A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3048 AN: 152228 Hom.: 116 Cov.: 33

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00778

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.00538 AC: 1324 AN: 245956 AF XY: 0.00407

Gnomad AFR exome AF: 0.0748

Gnomad AMR exome AF: 0.00374

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000180

Gnomad OTH exome AF: 0.00168

GnomAD4 exome AF: 0.00207 AC: 2944 AN: 1422990 Hom.: 98 Cov.: 26 AF XY: 0.00172 AC XY: 1222 AN XY: 710048

African (AFR) AF: 0.0721 AC: 2362 AN: 32770

American (AMR) AF: 0.00411 AC: 182 AN: 44238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25812

East Asian (EAS) AF: 0.00 AC: 0 AN: 39432

South Asian (SAS) AF: 0.000142 AC: 12 AN: 84516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00229 AC: 13 AN: 5686

European-Non Finnish (NFE) AF: 0.000114 AC: 123 AN: 1078228

Other (OTH) AF: 0.00427 AC: 252 AN: 59076

GnomAD4 genome AF: 0.0200 AC: 3054 AN: 152346 Hom.: 116 Cov.: 33 AF XY: 0.0187 AC XY: 1394 AN XY: 74508

African (AFR) AF: 0.0692 AC: 2878 AN: 41568

American (AMR) AF: 0.00777 AC: 119 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68036

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Alfa AF: 0.0120 Hom.: 9

Bravo AF: 0.0235

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.70
DANN	Benign	0.44
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11958721; hg19: chr5-13866284;