17-78427016-G-C

Variant names:

• chr17-78427016-G-C
• NM_173628.4:c.12681C>G

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_173628.4(DNAH17):​c.12681C>G​(p.Tyr4227*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH17 NM_173628.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423

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 Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.12681C>G	p.Tyr4227*	stop_gained	Exon 78 of 81	ENST00000389840.7	NP_775899.3
DNAH17	XM_011525416.3	c.12693C>G	p.Tyr4231*	stop_gained	Exon 78 of 81		XP_011523718.1
DNAH17	XM_024451013.2	c.12549C>G	p.Tyr4183*	stop_gained	Exon 77 of 80		XP_024306781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.12681C>G	p.Tyr4227*	stop_gained	Exon 78 of 81	5	NM_173628.4	ENSP00000374490.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	39
DANN	Uncertain	0.98
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.42	N
Vest4		0.29
GERP RS		-4.8

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: chr17-76423097;