rs7405830

chr17-78476686-G-A

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.8040C>T(p.Leu2680=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,611,882 control chromosomes in the GnomAD database, including 51,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (12352 hom., cov: 32)
  • Exomes 𝑓: 0.22 (39627 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.67

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=-0.72).
• BP6: Variant 17-78476686-G-A is Benign according to our data. Variant chr17-78476686-G-A is described in ClinVar as [Benign]. Clinvar id is 402679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.67 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH17	NM_173628.4	c.8040C>T	p.Leu2680=	synonymous_variant	52/81	ENST00000389840.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH17	ENST00000389840.7	c.8040C>T	p.Leu2680=	synonymous_variant	52/81	5	NM_173628.4	P1
DNAH17	ENST00000586052.5	n.1511-827C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52246 AN: 151914 Hom.: 12314 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.323

GnomAD3 exomes AF: 0.249 AC: 61240 AN: 246036 Hom.: 9284 AF XY: 0.243 AC XY: 32380 AN XY: 133442

Gnomad AFR exome AF: 0.695

Gnomad AMR exome AF: 0.230

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.289

Gnomad SAS exome AF: 0.249

Gnomad FIN exome AF: 0.206

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.229

GnomAD4 exome AF: 0.218 AC: 318529 AN: 1459850 Hom.: 39627 Cov.: 33 AF XY: 0.217 AC XY: 157603 AN XY: 726002

Gnomad4 AFR exome AF: 0.696

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.344 AC: 52330 AN: 152032 Hom.: 12352 Cov.: 32 AF XY: 0.342 AC XY: 25397 AN XY: 74338

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.324

Alfa AF: 0.231 Hom.: 9376

Bravo AF: 0.364

Asia WGS AF: 0.306 AC: 1067 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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, criteria provided, single submitter

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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	0.094
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs7405830; hg19: chr17-76472768; COSMIC: COSV67754473; COSMIC: COSV67754473;