17-78561780-T-C

Variant names:

• chr17-78561780-T-C
• rs894966
• NM_173628.4:c.1770A>G

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.1770A>G​(p.Lys590Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 1,613,294 control chromosomes in the GnomAD database, including 735,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68168 hom., cov: 32)
  • Exomes 𝑓: 0.96 (667207 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.538

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=-0.58).
• BP6: Variant 17-78561780-T-C is Benign according to our data. Variant chr17-78561780-T-C is described in ClinVar as [Benign]. Clinvar id is 402701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.538 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.1770A>G	p.Lys590Lys	synonymous_variant	Exon 12 of 81	ENST00000389840.7	NP_775899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.1770A>G	p.Lys590Lys	synonymous_variant	Exon 12 of 81	5	NM_173628.4	ENSP00000374490.6
DNAH17	ENST00000589793.1	n.982A>G		non_coding_transcript_exon_variant	Exon 8 of 13	2

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143946 AN: 152158 Hom.: 68131 Cov.: 32

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.953

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.962

Gnomad OTH AF: 0.946

GnomAD3 exomes AF: 0.946 AC: 235710 AN: 249200 Hom.: 111570 AF XY: 0.944 AC XY: 127410 AN XY: 134940

Gnomad AFR exome AF: 0.937

Gnomad AMR exome AF: 0.968

Gnomad ASJ exome AF: 0.936

Gnomad EAS exome AF: 0.911

Gnomad SAS exome AF: 0.928

Gnomad FIN exome AF: 0.899

Gnomad NFE exome AF: 0.961

Gnomad OTH exome AF: 0.951

GnomAD4 exome AF: 0.955 AC: 1395954 AN: 1461018 Hom.: 667207 Cov.: 71 AF XY: 0.954 AC XY: 693336 AN XY: 726732

Gnomad4 AFR exome AF: 0.936

Gnomad4 AMR exome AF: 0.964

Gnomad4 ASJ exome AF: 0.936

Gnomad4 EAS exome AF: 0.912

Gnomad4 SAS exome AF: 0.928

Gnomad4 FIN exome AF: 0.904

Gnomad4 NFE exome AF: 0.963

Gnomad4 OTH exome AF: 0.954

GnomAD4 genome AF: 0.946 AC: 144042 AN: 152276 Hom.: 68168 Cov.: 32 AF XY: 0.942 AC XY: 70164 AN XY: 74468

Gnomad4 AFR AF: 0.937

Gnomad4 AMR AF: 0.953

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.930

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.962

Gnomad4 OTH AF: 0.942

Alfa AF: 0.955 Hom.: 30049

Bravo AF: 0.952

Asia WGS AF: 0.926 AC: 3221 AN: 3478

EpiCase AF: 0.961

EpiControl AF: 0.959

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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: MAF -

DNAH17-related disorder Benign:1

Oct 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	-0.58
CADD	Benign	7.6
DANN	Benign	0.62

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: rs894966; hg19: chr17-76557862; COSMIC: COSV67758972;