rs691225

Variant names:

• chr17-78466688-G-A
• rs691225
• NM_173628.4:c.8907C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-78466688-G-A
• chr17-78466688-G-C

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.8907C>T​(p.Ser2969Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 1,611,012 control chromosomes in the GnomAD database, including 468,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (36293 hom., cov: 31)
  • Exomes 𝑓: 0.77 (432348 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.209

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=-0.82).
• BP6: Variant 17-78466688-G-A is Benign according to our data. Variant chr17-78466688-G-A is described in ClinVar as [Benign]. Clinvar id is 402677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.209 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.8907C>T	p.Ser2969Ser	synonymous_variant	Exon 56 of 81	ENST00000389840.7	NP_775899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.8907C>T	p.Ser2969Ser	synonymous_variant	Exon 56 of 81	5	NM_173628.4	ENSP00000374490.6
DNAH17	ENST00000586052.5	n.2289C>T		non_coding_transcript_exon_variant	Exon 12 of 35	5
DNAH17	ENST00000591369.5	n.507C>T		non_coding_transcript_exon_variant	Exon 3 of 28	5		ENSP00000466150.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101790 AN: 151894 Hom.: 36283 Cov.: 31

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.708

GnomAD3 exomes AF: 0.738 AC: 181658 AN: 246148 Hom.: 68407 AF XY: 0.737 AC XY: 98620 AN XY: 133798

Gnomad AFR exome AF: 0.387

Gnomad AMR exome AF: 0.779

Gnomad ASJ exome AF: 0.765

Gnomad EAS exome AF: 0.822

Gnomad SAS exome AF: 0.628

Gnomad FIN exome AF: 0.757

Gnomad NFE exome AF: 0.782

Gnomad OTH exome AF: 0.773

GnomAD4 exome AF: 0.766 AC: 1117628 AN: 1459000 Hom.: 432348 Cov.: 54 AF XY: 0.763 AC XY: 553377 AN XY: 725678

Gnomad4 AFR exome AF: 0.392

Gnomad4 AMR exome AF: 0.778

Gnomad4 ASJ exome AF: 0.765

Gnomad4 EAS exome AF: 0.819

Gnomad4 SAS exome AF: 0.626

Gnomad4 FIN exome AF: 0.754

Gnomad4 NFE exome AF: 0.787

Gnomad4 OTH exome AF: 0.754

GnomAD4 genome AF: 0.670 AC: 101822 AN: 152012 Hom.: 36293 Cov.: 31 AF XY: 0.670 AC XY: 49750 AN XY: 74294

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.830

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.710

Alfa AF: 0.731 Hom.: 22857

Bravo AF: 0.661

Asia WGS AF: 0.705 AC: 2448 AN: 3478

EpiCase AF: 0.780

EpiControl AF: 0.779

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	-0.82
CADD	Benign	0.037
DANN	Benign	0.34

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: rs691225; hg19: chr17-76462770; COSMIC: COSV67755373;