17-78532708-A-G

Position:

• chr17-78532708-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173628.4(DNAH17):​c.2888T>C​(p.Ile963Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,590,510 control chromosomes in the GnomAD database, including 211,095 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.51 (19651 hom., cov: 31)
  • Exomes 𝑓: 0.51 (191444 hom.)
• Consequence: DNAH17 NM_173628.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.338

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.5595555E-4).
• BP6: Variant 17-78532708-A-G is Benign according to our data. Variant chr17-78532708-A-G is described in ClinVar as [Benign]. Clinvar id is 402697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.2888T>C	p.Ile963Thr	missense_variant	20/81	ENST00000389840.7	NP_775899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.2888T>C	p.Ile963Thr	missense_variant	20/81	5	NM_173628.4	ENSP00000374490.6

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76780 AN: 151748 Hom.: 19642 Cov.: 31

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.520

GnomAD3 exomes AF: 0.481 AC: 104088 AN: 216402 Hom.: 25326 AF XY: 0.485 AC XY: 56587 AN XY: 116670

Gnomad AFR exome AF: 0.478

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.519

Gnomad EAS exome AF: 0.425

Gnomad SAS exome AF: 0.425

Gnomad FIN exome AF: 0.516

Gnomad NFE exome AF: 0.529

Gnomad OTH exome AF: 0.510

GnomAD4 exome AF: 0.514 AC: 740145 AN: 1438644 Hom.: 191444 Cov.: 48 AF XY: 0.513 AC XY: 365806 AN XY: 713286

Gnomad4 AFR exome AF: 0.483

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.522

Gnomad4 EAS exome AF: 0.439

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.529

Gnomad4 OTH exome AF: 0.513

GnomAD4 genome AF: 0.506 AC: 76821 AN: 151866 Hom.: 19651 Cov.: 31 AF XY: 0.502 AC XY: 37239 AN XY: 74210

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.517

Alfa AF: 0.497 Hom.: 9036

Bravo AF: 0.499

TwinsUK AF: 0.521 AC: 1932

ALSPAC AF: 0.529 AC: 2040

ESP6500AA AF: 0.499 AC: 1965

ESP6500EA AF: 0.531 AC: 4411

ExAC AF: 0.463 AC: 55419

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

DNAH17-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.9
DANN	Benign	0.60
DEOGEN2	Benign	0.0037	.;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.59	T;T
MetaRNN	Benign	0.00016	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.030	.;N
REVEL	Benign	0.062
Sift	Benign	0.65	.;T
Vest4		0.039
ClinPred		0.0076	T
GERP RS		3.0
Varity_R		0.062
gMVP		0.25

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: rs11651537; hg19: chr17-76528790; COSMIC: COSV67758202; COSMIC: COSV67758202;