rs35422926

Positions:

• chr17-78425383-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_173628.4(DNAH17):​c.13104G>A​(p.Pro4368=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,606 control chromosomes in the GnomAD database, including 23,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2446 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20603 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.942

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-78425383-C-T is Benign according to our data. Variant chr17-78425383-C-T is described in ClinVar as [Benign]. Clinvar id is 402670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.942 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.13104G>A	p.Pro4368=	synonymous_variant	80/81	ENST00000389840.7	NP_775899.3
DNAH17	XM_011525416.3	c.13116G>A	p.Pro4372=	synonymous_variant	80/81		XP_011523718.1
DNAH17	XM_024451013.2	c.12972G>A	p.Pro4324=	synonymous_variant	79/80		XP_024306781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.13104G>A	p.Pro4368=	synonymous_variant	80/81	5	NM_173628.4	ENSP00000374490	P1
DNAH17	ENST00000586052.5	n.6265G>A		non_coding_transcript_exon_variant	34/35	5
DNAH17	ENST00000590227.5	n.2778G>A		non_coding_transcript_exon_variant	12/13	2
DNAH17	ENST00000591369.5	c.*35G>A		3_prime_UTR_variant, NMD_transcript_variant	27/28	5		ENSP00000466150

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26288 AN: 151974 Hom.: 2443 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.179

GnomAD3 exomes AF: 0.150 AC: 37695 AN: 251026 Hom.: 3169 AF XY: 0.154 AC XY: 20877 AN XY: 135662

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.0905

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.0352

Gnomad SAS exome AF: 0.162

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.163 AC: 238682 AN: 1461514 Hom.: 20603 Cov.: 33 AF XY: 0.163 AC XY: 118595 AN XY: 727036

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.0931

Gnomad4 ASJ exome AF: 0.233

Gnomad4 EAS exome AF: 0.0217

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.173 AC: 26308 AN: 152092 Hom.: 2446 Cov.: 32 AF XY: 0.168 AC XY: 12512 AN XY: 74346

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.0305

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.177

Alfa AF: 0.180 Hom.: 1114

Bravo AF: 0.178

Asia WGS AF: 0.0790 AC: 274 AN: 3478

EpiCase AF: 0.168

EpiControl AF: 0.176

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

Nov 18, 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
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.88
DANN	Benign	0.92

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: rs35422926; hg19: chr17-76421464; COSMIC: COSV53145271; COSMIC: COSV53145271;