17-78495046-G-C

Variant names:

• chr17-78495046-G-C
• rs606944
• NM_173628.4:c.5955C>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.5955C>G​(p.Leu1985Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 1,610,586 control chromosomes in the GnomAD database, including 567,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (58070 hom., cov: 34)
  • Exomes 𝑓: 0.83 (509514 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.916

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 17-78495046-G-C is Benign according to our data. Variant chr17-78495046-G-C is described in ClinVar as [Benign]. Clinvar id is 402683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.916 with no splicing effect.
• 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 rank	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.5955C>G	p.Leu1985Leu	synonymous_variant	Exon 39 of 81	ENST00000389840.7	NP_775899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.5955C>G	p.Leu1985Leu	synonymous_variant	Exon 39 of 81	5	NM_173628.4	ENSP00000374490.6
DNAH17-AS1	ENST00000591373.2	n.769+849G>C		intron_variant	Intron 4 of 5	5

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132271 AN: 151950 Hom.: 58007 Cov.: 34

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.933

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.876

GnomAD3 exomes AF: 0.863 AC: 210518 AN: 243820 Hom.: 91400 AF XY: 0.861 AC XY: 114050 AN XY: 132498

Gnomad AFR exome AF: 0.971

Gnomad AMR exome AF: 0.916

Gnomad ASJ exome AF: 0.849

Gnomad EAS exome AF: 0.977

Gnomad SAS exome AF: 0.928

Gnomad FIN exome AF: 0.808

Gnomad NFE exome AF: 0.810

Gnomad OTH exome AF: 0.845

GnomAD4 exome AF: 0.834 AC: 1217101 AN: 1458518 Hom.: 509514 Cov.: 66 AF XY: 0.836 AC XY: 606050 AN XY: 725304

Gnomad4 AFR exome AF: 0.975

Gnomad4 AMR exome AF: 0.913

Gnomad4 ASJ exome AF: 0.849

Gnomad4 EAS exome AF: 0.988

Gnomad4 SAS exome AF: 0.926

Gnomad4 FIN exome AF: 0.810

Gnomad4 NFE exome AF: 0.814

Gnomad4 OTH exome AF: 0.852

GnomAD4 genome AF: 0.871 AC: 132394 AN: 152068 Hom.: 58070 Cov.: 34 AF XY: 0.873 AC XY: 64872 AN XY: 74298

Gnomad4 AFR AF: 0.968

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.978

Gnomad4 SAS AF: 0.932

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.878

Alfa AF: 0.816 Hom.: 13045

Bravo AF: 0.881

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

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: Frequency -

DNAH17-related disorder Benign:1

Oct 17, 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	-0.55
CADD	Benign	5.2
DANN	Benign	0.81

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: rs606944; hg19: chr17-76491128; COSMIC: COSV67758966; COSMIC: COSV67758966;