17-11598503-G-C

Variant names:

• chr17-11598503-G-C
• NM_001372.4:c.5G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001372.4(DNAH9):​c.5G>C​(p.Arg2Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000829 in 1,206,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: DNAH9 NM_001372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776

Genes affected

DNAH9 (HGNC:2953): (dynein axonemal heavy chain 9) This gene encodes the heavy chain subunit of axonemal dynein, a large multi-subunit molecular motor. Axonemal dynein attaches to microtubules and hydrolyzes ATP to mediate the movement of cilia and flagella. The gene expresses at least two transcript variants; additional variants have been described, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06426951).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH9	NM_001372.4	c.5G>C	p.Arg2Pro	missense_variant	Exon 1 of 69	ENST00000262442.9	NP_001363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9	c.5G>C	p.Arg2Pro	missense_variant	Exon 1 of 69	1	NM_001372.4	ENSP00000262442.3
DNAH9	ENST00000579406.1	n.32G>C		non_coding_transcript_exon_variant	Exon 1 of 8	1
DNAH9	ENST00000454412.6	c.5G>C	p.Arg2Pro	missense_variant	Exon 1 of 68	5		ENSP00000414874.2
DNAH9	ENST00000579828.5	c.5G>C	p.Arg2Pro	missense_variant	Exon 1 of 4	2		ENSP00000463782.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.29e-7 AC: 1 AN: 1206482 Hom.: 0 Cov.: 33 AF XY: 0.00000171 AC XY: 1 AN XY: 586434

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000201

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.4
DANN	Benign	0.40
DEOGEN2	Benign	0.0062	T;.;.
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0084	N
LIST_S2	Benign	0.39	T;T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.064	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.1	N;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.60	N;.;N
REVEL	Benign	0.036
Sift	Benign	0.50	T;.;T
Sift4G	Benign	0.26	.;T;.
Polyphen		0.0	B;.;B
Vest4		0.082
MutPred		0.39		Gain of catalytic residue at R2 (P = 0.0052);Gain of catalytic residue at R2 (P = 0.0052);Gain of catalytic residue at R2 (P = 0.0052);
MVP		0.18
MPC		0.13
ClinPred		0.035	T
GERP RS		-6.6
Varity_R		0.069
gMVP		0.20

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-11501820;