5-13940955-A-G

Variant names:

• chr5-13940955-A-G
• rs2582683
• NM_001369.3:c.57+3427T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369.3(DNAH5):​c.57+3427T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 152,210 control chromosomes in the GnomAD database, including 56,666 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (56666 hom., cov: 32)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.903 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.57+3427T>C		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.57+3427T>C		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.13-9711T>C		intron	N/A	ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130788 AN: 152092 Hom.: 56633 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.859

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

GnomAD4 genome AF: 0.860 AC: 130871 AN: 152210 Hom.: 56666 Cov.: 32 AF XY: 0.861 AC XY: 64087 AN XY: 74426

African (AFR) AF: 0.748 AC: 31044 AN: 41530

American (AMR) AF: 0.886 AC: 13555 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.922 AC: 3201 AN: 3470

East Asian (EAS) AF: 0.846 AC: 4362 AN: 5158

South Asian (SAS) AF: 0.854 AC: 4111 AN: 4812

European-Finnish (FIN) AF: 0.925 AC: 9809 AN: 10602

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.909 AC: 61849 AN: 68024

Other (OTH) AF: 0.861 AC: 1821 AN: 2114

Alfa AF: 0.893 Hom.: 42002

Bravo AF: 0.854

Asia WGS AF: 0.848 AC: 2949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.017
DANN	Benign	0.44
PhyloP100		-1.6
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: rs2582683; hg19: chr5-13941064;