rs795527

Variant names:

• chr5-13850622-C-A
• rs795527
• NM_001369.3:c.5114+30G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-13850622-C-A
• chr5-13850622-C-G
• chr5-13850622-C-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.5114+30G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0515 in 1,601,962 control chromosomes in the GnomAD database, including 2,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (309 hom., cov: 33)
  • Exomes 𝑓: 0.050 (2130 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.05
• Publications: 3 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• 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=-0.86).
• BP6: Variant 5-13850622-C-A is Benign according to our data. Variant chr5-13850622-C-A is described in ClinVar as Benign. ClinVar VariationId is 258039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.077 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.5114+30G>T		intron	N/A	NP_001360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.5114+30G>T		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.5069+30G>T		intron	N/A	ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9378 AN: 152044 Hom.: 308 Cov.: 33

Gnomad AFR AF: 0.0792

Gnomad AMI AF: 0.0496

Gnomad AMR AF: 0.0670

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.0289

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.0511

GnomAD2 exomes AF: 0.0564 AC: 14140 AN: 250760 AF XY: 0.0523

Gnomad AFR exome AF: 0.0832

Gnomad AMR exome AF: 0.0942

Gnomad ASJ exome AF: 0.0425

Gnomad EAS exome AF: 0.0326

Gnomad FIN exome AF: 0.0967

Gnomad NFE exome AF: 0.0462

Gnomad OTH exome AF: 0.0447

GnomAD4 exome AF: 0.0504 AC: 73118 AN: 1449800 Hom.: 2130 Cov.: 27 AF XY: 0.0493 AC XY: 35586 AN XY: 722146

African (AFR) AF: 0.0808 AC: 2692 AN: 33298

American (AMR) AF: 0.0923 AC: 4125 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.0469 AC: 1223 AN: 26052

East Asian (EAS) AF: 0.0256 AC: 1013 AN: 39628

South Asian (SAS) AF: 0.0321 AC: 2754 AN: 85906

European-Finnish (FIN) AF: 0.0920 AC: 4908 AN: 53360

Middle Eastern (MID) AF: 0.0146 AC: 80 AN: 5498

European-Non Finnish (NFE) AF: 0.0485 AC: 53464 AN: 1101398

Other (OTH) AF: 0.0477 AC: 2859 AN: 59972

GnomAD4 genome AF: 0.0617 AC: 9393 AN: 152162 Hom.: 309 Cov.: 33 AF XY: 0.0630 AC XY: 4684 AN XY: 74390

African (AFR) AF: 0.0793 AC: 3290 AN: 41502

American (AMR) AF: 0.0672 AC: 1026 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3466

East Asian (EAS) AF: 0.0332 AC: 172 AN: 5182

South Asian (SAS) AF: 0.0293 AC: 141 AN: 4810

European-Finnish (FIN) AF: 0.104 AC: 1108 AN: 10606

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0492 AC: 3344 AN: 68000

Other (OTH) AF: 0.0506 AC: 107 AN: 2116

Alfa AF: 0.0344 Hom.: 33

Bravo AF: 0.0598

ClinVar

ClinVar submissions as Germline

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	-0.86
CADD	Benign	0.0050
DANN	Benign	0.66
PhyloP100		-2.0
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: rs795527; hg19: chr5-13850731;