chr17-11640293-A-C

Position:

• chr17-11640293-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000262442.9(DNAH9):​c.1810A>C​(p.Met604Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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. M604V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH9 ENST00000262442.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.88

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41800207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH9	NM_001372.4	c.1810A>C	p.Met604Leu	missense_variant	10/69	ENST00000262442.9	NP_001363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9	c.1810A>C	p.Met604Leu	missense_variant	10/69	1	NM_001372.4	ENSP00000262442	P1
DNAH9	ENST00000454412.6	c.1810A>C	p.Met604Leu	missense_variant	10/68	5		ENSP00000414874

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	0.24
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.043	T;.
Eigen	Benign	0.054
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	0.95	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.19
Sift	Benign	0.35	T;T
Polyphen		0.11	B;.
Vest4		0.53
MutPred		0.54		Loss of catalytic residue at V600 (P = 0.0154);Loss of catalytic residue at V600 (P = 0.0154);
MVP		0.72
MPC		0.086
ClinPred		0.58	D
GERP RS		5.4
Varity_R		0.28
gMVP		0.29

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

LitVar

Other links and lift over

dbSNP: rs61740059; hg19: chr17-11543610;