rs691652

Positions:

• chr17-78495045-T-C

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.5956A>G​(p.Met1986Val) variant causes a missense change. The variant allele was found at a frequency of 0.838 in 1,610,590 control chromosomes in the GnomAD database, including 568,113 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (58109 hom., cov: 34)
  • Exomes 𝑓: 0.83 (510004 hom.)
• Consequence: DNAH17 NM_173628.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 5.96

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]

DNAH17-AS1 (HGNC:48594): (DNAH17 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.9940725E-7).
• BP6: Variant 17-78495045-T-C is Benign according to our data. Variant chr17-78495045-T-C is described in ClinVar as [Benign]. Clinvar id is 402682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH17	NM_173628.4	c.5956A>G	p.Met1986Val	missense_variant	39/81	ENST00000389840.7
DNAH17-AS1	NR_102401.1	n.769+848T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH17	ENST00000389840.7	c.5956A>G	p.Met1986Val	missense_variant	39/81	5	NM_173628.4	P1
DNAH17-AS1	ENST00000591373.2	n.769+848T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132319 AN: 151944 Hom.: 58046 Cov.: 34

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.877

GnomAD3 exomes AF: 0.864 AC: 210604 AN: 243816 Hom.: 91474 AF XY: 0.861 AC XY: 114096 AN XY: 132504

Gnomad AFR exome AF: 0.971

Gnomad AMR exome AF: 0.916

Gnomad ASJ exome AF: 0.851

Gnomad EAS exome AF: 0.977

Gnomad SAS exome AF: 0.928

Gnomad FIN exome AF: 0.809

Gnomad NFE exome AF: 0.810

Gnomad OTH exome AF: 0.846

GnomAD4 exome AF: 0.835 AC: 1217715 AN: 1458528 Hom.: 510004 Cov.: 66 AF XY: 0.836 AC XY: 606370 AN XY: 725306

Gnomad4 AFR exome AF: 0.975

Gnomad4 AMR exome AF: 0.913

Gnomad4 ASJ exome AF: 0.851

Gnomad4 EAS exome AF: 0.988

Gnomad4 SAS exome AF: 0.926

Gnomad4 FIN exome AF: 0.811

Gnomad4 NFE exome AF: 0.815

Gnomad4 OTH exome AF: 0.852

GnomAD4 genome AF: 0.871 AC: 132442 AN: 152062 Hom.: 58109 Cov.: 34 AF XY: 0.873 AC XY: 64892 AN XY: 74298

Gnomad4 AFR AF: 0.968

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.858

Gnomad4 EAS AF: 0.978

Gnomad4 SAS AF: 0.932

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.808

Gnomad4 OTH AF: 0.879

Alfa AF: 0.827 Hom.: 80354

Bravo AF: 0.881

TwinsUK AF: 0.819 AC: 3038

ALSPAC AF: 0.816 AC: 3144

ESP6500AA AF: 0.971 AC: 3968

ESP6500EA AF: 0.814 AC: 6834

ExAC AF: 0.857 AC: 103527

Asia WGS AF: 0.965 AC: 3357 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

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	0.041
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.52
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.60	T;T
MetaRNN	Benign	8.0e-7	T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	0.81	P;P
PrimateAI	Uncertain	0.78	T
REVEL	Benign	0.092
Vest4		0.090
ClinPred		0.014	T
GERP RS		3.8
Varity_R		0.10
gMVP		0.48

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: rs691652; hg19: chr17-76491127; COSMIC: COSV67758961; COSMIC: COSV67758961;