Genetic Variant DNAH17:c.7275+45A>G (chr17-78485915-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173628.4(DNAH17):c.7275+45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,597,128 control chromosomes in the GnomAD database, including 360,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33282 hom., cov: 31)

Exomes 𝑓: 0.67 ( 327650 hom. )

Consequence

DNAH17
NM_173628.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.104

Variant links:

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 links:

DNAH17-AS1 (HGNC:48594): (DNAH17 antisense RNA 1)

DNAH17-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-78485915-T-C is Benign according to our data. Variant chr17-78485915-T-C is described in ClinVar as [Benign]. Clinvar id is 1263686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.7275+45A>G		intron_variant	Intron 46 of 80	ENST00000389840.7	NP_775899.3	Q9UFH2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7 link	c.7275+45A>G		intron_variant	Intron 46 of 80	5	NM_173628.4	ENSP00000374490.6		Q9UFH2-1

Frequencies

GnomAD3 genomes

AF:

0.659

AC:

100002

AN:

151798

Hom.:

33256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.596

Gnomad AMI

AF:

0.670

Gnomad AMR

AF:

0.740

Gnomad ASJ

AF:

0.689

Gnomad EAS

AF:

0.637

Gnomad SAS

AF:

0.735

Gnomad FIN

AF:

0.678

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.670

Gnomad OTH

AF:

0.675

GnomAD3 exomes

AF:

0.692

AC:

163203

AN:

235892

Hom.:

56852

AF XY:

0.692

AC XY:

88743

AN XY:

128178

show subpopulations

Gnomad AFR exome

AF:

0.596

Gnomad AMR exome

AF:

0.793

Gnomad ASJ exome

AF:

0.680

Gnomad EAS exome

AF:

0.642

Gnomad SAS exome

AF:

0.749

Gnomad FIN exome

AF:

0.667

Gnomad NFE exome

AF:

0.672

Gnomad OTH exome

AF:

0.688

GnomAD4 exome

AF:

0.672

AC:

971501

AN:

1445212

Hom.:

327650

Cov.:

AF XY:

0.674

AC XY:

483787

AN XY:

718178

show subpopulations

Gnomad4 AFR exome

AF:

0.594

Gnomad4 AMR exome

AF:

0.785

Gnomad4 ASJ exome

AF:

0.675

Gnomad4 EAS exome

AF:

0.642

Gnomad4 SAS exome

AF:

0.747

Gnomad4 FIN exome

AF:

0.670

Gnomad4 NFE exome

AF:

0.666

Gnomad4 OTH exome

AF:

0.668

GnomAD4 genome

AF:

0.659

AC:

100081

AN:

151916

Hom.:

33282

Cov.:

AF XY:

0.662

AC XY:

49130

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.596

Gnomad4 AMR

AF:

0.740

Gnomad4 ASJ

AF:

0.689

Gnomad4 EAS

AF:

0.636

Gnomad4 SAS

AF:

0.736

Gnomad4 FIN

AF:

0.678

Gnomad4 NFE

AF:

0.670

Gnomad4 OTH

AF:

0.677

Alfa

AF:

0.635

Hom.:

6750

Bravo

AF:

0.661

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.74

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over