NM_001369.3:c.5114+11T>C

Variant names:

• chr5-13850641-A-G
• rs6554820
• NM_001369.3:c.5114+11T>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.5114+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,611,744 control chromosomes in the GnomAD database, including 134,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10926 hom., cov: 32)
  • Exomes 𝑓: 0.41 (123985 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0310
• Publications: 7 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 5-13850641-A-G is Benign according to our data. Variant chr5-13850641-A-G is described in ClinVar as Benign. ClinVar VariationId is 163150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.454 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.5114+11T>C		intron	N/A	NP_001360.1	Q8TE73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.5114+11T>C		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.5069+11T>C		intron	N/A	ENSP00000505288.1	A0A7P0Z455

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56828 AN: 152042 Hom.: 10906 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.375

GnomAD2 exomes AF: 0.384 AC: 96355 AN: 250974 AF XY: 0.393

Gnomad AFR exome AF: 0.294

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.239

Gnomad FIN exome AF: 0.455

Gnomad NFE exome AF: 0.420

Gnomad OTH exome AF: 0.373

GnomAD4 exome AF: 0.409 AC: 596546 AN: 1459584 Hom.: 123985 Cov.: 34 AF XY: 0.411 AC XY: 298258 AN XY: 726280

African (AFR) AF: 0.306 AC: 10245 AN: 33430

American (AMR) AF: 0.283 AC: 12645 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 8620 AN: 26128

East Asian (EAS) AF: 0.259 AC: 10276 AN: 39658

South Asian (SAS) AF: 0.472 AC: 40653 AN: 86178

European-Finnish (FIN) AF: 0.455 AC: 24278 AN: 53394

Middle Eastern (MID) AF: 0.339 AC: 1906 AN: 5618

European-Non Finnish (NFE) AF: 0.418 AC: 464247 AN: 1110140

Other (OTH) AF: 0.392 AC: 23676 AN: 60326

GnomAD4 genome AF: 0.374 AC: 56890 AN: 152160 Hom.: 10926 Cov.: 32 AF XY: 0.373 AC XY: 27763 AN XY: 74392

African (AFR) AF: 0.303 AC: 12578 AN: 41518

American (AMR) AF: 0.314 AC: 4805 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1122 AN: 3468

East Asian (EAS) AF: 0.263 AC: 1361 AN: 5178

South Asian (SAS) AF: 0.470 AC: 2257 AN: 4804

European-Finnish (FIN) AF: 0.463 AC: 4903 AN: 10598

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28659 AN: 67984

Other (OTH) AF: 0.379 AC: 799 AN: 2110

Alfa AF: 0.398 Hom.: 27373

Bravo AF: 0.355

Asia WGS AF: 0.388 AC: 1352 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Primary ciliary dyskinesia 3 (3)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.3
DANN	Benign	0.69
PhyloP100		-0.031
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: rs6554820; hg19: chr5-13850750; COSMIC: COSV54227289;