rs1554058022

chr5-13809117-C-Gchr5-13809117-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001369.3(DNAH5):c.7679G>C(p.Gly2560Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G2560D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH5 NM_001369.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08775514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.7679G>C	p.Gly2560Ala	missense_variant	46/79	ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.7679G>C	p.Gly2560Ala	missense_variant	46/79	1	NM_001369.3	P4
DNAH5	ENST00000681290.1	c.7634G>C	p.Gly2545Ala	missense_variant	46/79			A1
DNAH5	ENST00000512443.1	n.535G>C		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	16
Dann	Benign	0.42
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.86	N
MutationTaster	Benign	0.66	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.089
Sift	Benign	0.92	T
Polyphen		0.0	B
Vest4		0.26
MutPred		0.41		Gain of helix (P = 0.0425);
MVP		0.31
MPC		0.48
ClinPred		0.26	T
GERP RS		5.0
Varity_R		0.057
gMVP		0.48

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-13809226;