chr17-78507511-T-C

Position:

• chr17-78507511-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.4531A>G​(p.Thr1511Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,613,342 control chromosomes in the GnomAD database, including 301,130 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (30346 hom., cov: 34)
  • Exomes 𝑓: 0.61 (270784 hom.)
• Consequence: DNAH17 NM_173628.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.117

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=7.406597E-7).
• BP6: Variant 17-78507511-T-C is Benign according to our data. Variant chr17-78507511-T-C is described in ClinVar as [Benign]. Clinvar id is 402690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.4531A>G	p.Thr1511Ala	missense_variant	28/81	ENST00000389840.7	NP_775899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.4531A>G	p.Thr1511Ala	missense_variant	28/81	5	NM_173628.4	ENSP00000374490	P1
DNAH17	ENST00000587177.1	n.583A>G		non_coding_transcript_exon_variant	2/7	5

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94855 AN: 152032 Hom.: 30319 Cov.: 34

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.631

GnomAD3 exomes AF: 0.563 AC: 140036 AN: 248814 Hom.: 40972 AF XY: 0.568 AC XY: 76683 AN XY: 134990

Gnomad AFR exome AF: 0.732

Gnomad AMR exome AF: 0.359

Gnomad ASJ exome AF: 0.650

Gnomad EAS exome AF: 0.463

Gnomad SAS exome AF: 0.535

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.615

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.605 AC: 884358 AN: 1461192 Hom.: 270784 Cov.: 89 AF XY: 0.603 AC XY: 438577 AN XY: 726794

Gnomad4 AFR exome AF: 0.737

Gnomad4 AMR exome AF: 0.374

Gnomad4 ASJ exome AF: 0.648

Gnomad4 EAS exome AF: 0.477

Gnomad4 SAS exome AF: 0.539

Gnomad4 FIN exome AF: 0.568

Gnomad4 NFE exome AF: 0.620

Gnomad4 OTH exome AF: 0.614

GnomAD4 genome AF: 0.624 AC: 94929 AN: 152150 Hom.: 30346 Cov.: 34 AF XY: 0.617 AC XY: 45870 AN XY: 74360

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.626

Alfa AF: 0.622 Hom.: 48081

Bravo AF: 0.623

TwinsUK AF: 0.619 AC: 2294

ALSPAC AF: 0.625 AC: 2408

ESP6500AA AF: 0.736 AC: 3068

ESP6500EA AF: 0.614 AC: 5214

ExAC AF: 0.573 AC: 69344

Asia WGS AF: 0.540 AC: 1881 AN: 3478

EpiCase AF: 0.619

EpiControl AF: 0.621

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	0.056
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.24
DANN	Benign	0.39
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.44	T;T
MetaRNN	Benign	7.4e-7	T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.36	T
REVEL	Benign	0.041
Vest4		0.014
ClinPred		0.00030	T
GERP RS		1.6
Varity_R		0.050
gMVP		0.11

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: rs9896398; hg19: chr17-76503593; COSMIC: COSV67751281; COSMIC: COSV67751281;