rs7715811

Variant names:

• chr5-13769865-C-T
• rs7715811
• NM_001369.3:c.9606-250G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-13769865-C-T
• chr5-13769865-C-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001369.3(DNAH5):​c.9606-250G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,086 control chromosomes in the GnomAD database, including 7,936 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7936 hom., cov: 33)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.514
• Publications: 12 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-13769865-C-T is Benign according to our data. Variant chr5-13769865-C-T is described in ClinVar as Benign. ClinVar VariationId is 1271906.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 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.9606-250G>A		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.9606-250G>A		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.9561-250G>A		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000504001.3	TSL:5	n.318-250G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47375 AN: 151966 Hom.: 7914 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.280

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.312 AC: 47448 AN: 152086 Hom.: 7936 Cov.: 33 AF XY: 0.319 AC XY: 23698 AN XY: 74328

African (AFR) AF: 0.380 AC: 15747 AN: 41464

American (AMR) AF: 0.271 AC: 4141 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3472

East Asian (EAS) AF: 0.113 AC: 587 AN: 5176

South Asian (SAS) AF: 0.440 AC: 2123 AN: 4822

European-Finnish (FIN) AF: 0.443 AC: 4676 AN: 10566

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18653 AN: 68004

Other (OTH) AF: 0.284 AC: 599 AN: 2110

Alfa AF: 0.274 Hom.: 14455

Bravo AF: 0.295

Asia WGS AF: 0.328 AC: 1138 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.69
PhyloP100		-0.51
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: rs7715811; hg19: chr5-13769974;