17-78561780-T-G

Position:

• chr17-78561780-T-G

Variant summary

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

The NM_173628.4(DNAH17):​c.1770A>C​(p.Lys590Asn) 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. 11/19 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)
• Consequence: DNAH17 NM_173628.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.538

Genes affected

DNAH17 (HGNC:2946): (dynein axonemal heavy chain 17) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. DNAH17 is a heavy chain associated with axonemal dynein (Milisav and Affara, 1998 [PubMed 9545504]).[supplied by OMIM, Mar 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=0.41012543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.1770A>C	p.Lys590Asn	missense_variant	12/81	ENST00000389840.7	NP_775899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.1770A>C	p.Lys590Asn	missense_variant	12/81	5	NM_173628.4	ENSP00000374490	P1
DNAH17	ENST00000589793.1	n.982A>C		non_coding_transcript_exon_variant	8/13	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.8	.;M
MutationTaster	Benign	0.82	N;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.6	.;D
REVEL	Benign	0.22
Sift	Benign	0.15	.;T
Vest4		0.61
MVP		0.19
ClinPred		0.38	T
GERP RS		1.3
Varity_R		0.19
gMVP		0.34

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: rs894966; hg19: chr17-76557862;