rs1530497

Variant names:

• chr5-13931096-G-C
• rs1530497
• NM_001369.3:c.192+14C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-13931096-G-C
• chr5-13931096-G-A
• chr5-13931096-G-T

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.192+14C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,613,588 control chromosomes in the GnomAD database, including 94,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14517 hom., cov: 32)
  • Exomes 𝑓: 0.32 (79583 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.104
• Publications: 6 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=-0.88).
• BP6: Variant 5-13931096-G-C is Benign according to our data. Variant chr5-13931096-G-C is described in ClinVar as Benign. ClinVar VariationId is 163161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 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.192+14C>G		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.192+14C>G		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.147+14C>G		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000508040.1	TSL:2	n.551+14C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62445 AN: 151946 Hom.: 14494 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.409

GnomAD2 exomes AF: 0.371 AC: 93177 AN: 251132 AF XY: 0.361

Gnomad AFR exome AF: 0.618

Gnomad AMR exome AF: 0.424

Gnomad ASJ exome AF: 0.339

Gnomad EAS exome AF: 0.692

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.318 AC: 464938 AN: 1461524 Hom.: 79583 Cov.: 39 AF XY: 0.318 AC XY: 230910 AN XY: 727104

African (AFR) AF: 0.622 AC: 20805 AN: 33462

American (AMR) AF: 0.425 AC: 19009 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 8961 AN: 26126

East Asian (EAS) AF: 0.682 AC: 27073 AN: 39674

South Asian (SAS) AF: 0.357 AC: 30799 AN: 86250

European-Finnish (FIN) AF: 0.277 AC: 14783 AN: 53416

Middle Eastern (MID) AF: 0.326 AC: 1879 AN: 5766

European-Non Finnish (NFE) AF: 0.289 AC: 321236 AN: 1111736

Other (OTH) AF: 0.338 AC: 20393 AN: 60378

GnomAD4 genome AF: 0.411 AC: 62520 AN: 152064 Hom.: 14517 Cov.: 32 AF XY: 0.410 AC XY: 30457 AN XY: 74354

African (AFR) AF: 0.612 AC: 25369 AN: 41456

American (AMR) AF: 0.397 AC: 6053 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3468

East Asian (EAS) AF: 0.691 AC: 3572 AN: 5168

South Asian (SAS) AF: 0.374 AC: 1800 AN: 4810

European-Finnish (FIN) AF: 0.284 AC: 3011 AN: 10584

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.298 AC: 20285 AN: 67998

Other (OTH) AF: 0.408 AC: 861 AN: 2110

Alfa AF: 0.338 Hom.: 1738

Bravo AF: 0.428

Asia WGS AF: 0.511 AC: 1774 AN: 3476

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 (3)
-	-	2	not provided (2)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.34
PhyloP100		-0.10
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: rs1530497; hg19: chr5-13931205;