17-78453423-G-C

Variant names:

• chr17-78453423-G-C
• rs2289751
• NM_173628.4:c.10449C>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.10449C>G​(p.Thr3483Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,613,054 control chromosomes in the GnomAD database, including 241,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19086 hom., cov: 34)
  • Exomes 𝑓: 0.55 (222241 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.319

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=-0.51).
• BP6: Variant 17-78453423-G-C is Benign according to our data. Variant chr17-78453423-G-C is described in ClinVar as [Benign]. Clinvar id is 402676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.319 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.10449C>G	p.Thr3483Thr	synonymous_variant	Exon 65 of 81	ENST00000389840.7	NP_775899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.10449C>G	p.Thr3483Thr	synonymous_variant	Exon 65 of 81	5	NM_173628.4	ENSP00000374490.6
DNAH17	ENST00000586052.5	n.3734C>G		non_coding_transcript_exon_variant	Exon 20 of 35	5
DNAH17	ENST00000591369.5	n.2049C>G		non_coding_transcript_exon_variant	Exon 12 of 28	5		ENSP00000466150.1
DNAH17	ENST00000592152.1	n.796C>G		non_coding_transcript_exon_variant	Exon 4 of 5	5

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74539 AN: 152064 Hom.: 19072 Cov.: 34

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.527

GnomAD3 exomes AF: 0.521 AC: 130131 AN: 249610 Hom.: 34668 AF XY: 0.524 AC XY: 70720 AN XY: 134946

Gnomad AFR exome AF: 0.326

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.585

Gnomad EAS exome AF: 0.641

Gnomad SAS exome AF: 0.415

Gnomad FIN exome AF: 0.537

Gnomad NFE exome AF: 0.559

Gnomad OTH exome AF: 0.563

GnomAD4 exome AF: 0.548 AC: 801073 AN: 1460872 Hom.: 222241 Cov.: 48 AF XY: 0.545 AC XY: 396122 AN XY: 726668

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.486

Gnomad4 ASJ exome AF: 0.588

Gnomad4 EAS exome AF: 0.605

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.542

Gnomad4 NFE exome AF: 0.564

Gnomad4 OTH exome AF: 0.553

GnomAD4 genome AF: 0.490 AC: 74573 AN: 152182 Hom.: 19086 Cov.: 34 AF XY: 0.489 AC XY: 36414 AN XY: 74396

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.532

Alfa AF: 0.544 Hom.: 7419

Bravo AF: 0.485

Asia WGS AF: 0.506 AC: 1761 AN: 3478

EpiCase AF: 0.562

EpiControl AF: 0.582

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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	-0.51
CADD	Benign	4.4
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: rs2289751; hg19: chr17-76449505; COSMIC: COSV67754933; COSMIC: COSV67754933;