rs149460805

Variant names:

• chr5-13809034-A-G
• rs149460805
• NM_001369.3:c.7752+10T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-13809034-A-G
• chr5-13809034-A-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001369.3(DNAH5):​c.7752+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000418 in 1,614,052 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0023 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (2 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: 1.31
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 5-13809034-A-G is Benign according to our data. Variant chr5-13809034-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 197541.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00228 (347/152338) while in subpopulation AFR AF = 0.00811 (337/41568). AF 95% confidence interval is 0.00739. There are 3 homozygotes in GnomAd4. There are 172 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AD,AR gene

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.7752+10T>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.7752+10T>C		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.7707+10T>C		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000512443.1	TSL:3	n.608+10T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00228 AC: 347 AN: 152220 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00813

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000589 AC: 148 AN: 251470 AF XY: 0.000397

Gnomad AFR exome AF: 0.00806

Gnomad AMR exome AF: 0.000492

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000224 AC: 327 AN: 1461714 Hom.: 2 Cov.: 31 AF XY: 0.000199 AC XY: 145 AN XY: 727154

African (AFR) AF: 0.00824 AC: 276 AN: 33478

American (AMR) AF: 0.000402 AC: 18 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111872

Other (OTH) AF: 0.000497 AC: 30 AN: 60392

GnomAD4 genome AF: 0.00228 AC: 347 AN: 152338 Hom.: 3 Cov.: 32 AF XY: 0.00231 AC XY: 172 AN XY: 74496

African (AFR) AF: 0.00811 AC: 337 AN: 41568

American (AMR) AF: 0.000457 AC: 7 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00189 Hom.: 1

Bravo AF: 0.00260

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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: rs149460805; hg19: chr5-13809143;