chr17-78501838-C-A

Variant names:

• chr17-78501838-C-A
• rs690844
• NM_173628.4:c.5226G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173628.4(DNAH17):​c.5226G>T​(p.Met1742Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 1,613,752 control chromosomes in the GnomAD database, including 343,917 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (34233 hom., cov: 33)
  • Exomes 𝑓: 0.65 (309684 hom.)
• Consequence: DNAH17 NM_173628.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.43
• Publications: 34 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.7439837E-7).
• BP6: Variant 17-78501838-C-A is Benign according to our data. Variant chr17-78501838-C-A is described in ClinVar as Benign. ClinVar VariationId is 402686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173628.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	NM_173628.4	MANE Select	c.5226G>T	p.Met1742Ile	missense	Exon 34 of 81	NP_775899.3
	DNAH17-AS1	NR_102401.1		n.3945C>A		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.5226G>T	p.Met1742Ile	missense	Exon 34 of 81	ENSP00000374490.6
	DNAH17-AS1	ENST00000598378.2	TSL:2	n.3379C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101338 AN: 152022 Hom.: 34195 Cov.: 33

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.670

GnomAD2 exomes AF: 0.691 AC: 172182 AN: 249262 AF XY: 0.683

Gnomad AFR exome AF: 0.687

Gnomad AMR exome AF: 0.813

Gnomad ASJ exome AF: 0.652

Gnomad EAS exome AF: 0.952

Gnomad FIN exome AF: 0.677

Gnomad NFE exome AF: 0.617

Gnomad OTH exome AF: 0.659

GnomAD4 exome AF: 0.647 AC: 945213 AN: 1461612 Hom.: 309684 Cov.: 65 AF XY: 0.647 AC XY: 470506 AN XY: 727082

African (AFR) AF: 0.693 AC: 23203 AN: 33476

American (AMR) AF: 0.805 AC: 35997 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 17073 AN: 26134

East Asian (EAS) AF: 0.966 AC: 38356 AN: 39700

South Asian (SAS) AF: 0.700 AC: 60346 AN: 86258

European-Finnish (FIN) AF: 0.675 AC: 36021 AN: 53346

Middle Eastern (MID) AF: 0.625 AC: 3606 AN: 5768

European-Non Finnish (NFE) AF: 0.621 AC: 690857 AN: 1111840

Other (OTH) AF: 0.659 AC: 39754 AN: 60368

GnomAD4 genome AF: 0.667 AC: 101428 AN: 152140 Hom.: 34233 Cov.: 33 AF XY: 0.671 AC XY: 49927 AN XY: 74378

African (AFR) AF: 0.687 AC: 28531 AN: 41508

American (AMR) AF: 0.733 AC: 11214 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2262 AN: 3468

East Asian (EAS) AF: 0.949 AC: 4910 AN: 5174

South Asian (SAS) AF: 0.710 AC: 3423 AN: 4822

European-Finnish (FIN) AF: 0.671 AC: 7112 AN: 10596

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41823 AN: 67960

Other (OTH) AF: 0.673 AC: 1423 AN: 2114

Alfa AF: 0.640 Hom.: 129666

Bravo AF: 0.675

TwinsUK AF: 0.642 AC: 2379

ALSPAC AF: 0.619 AC: 2385

ESP6500AA AF: 0.695 AC: 3042

ESP6500EA AF: 0.616 AC: 5283

ExAC AF: 0.682 AC: 82618

Asia WGS AF: 0.800 AC: 2781 AN: 3478

EpiCase AF: 0.613

EpiControl AF: 0.609

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DNAH17-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0020
DANN	Benign	0.86
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	5.7e-7	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.4
PrimateAI	Uncertain	0.52	T
REVEL	Benign	0.0060
Vest4		0.037
ClinPred		0.000081	T
GERP RS		-2.5
Varity_R		0.12
gMVP		0.10
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs690844; hg19: chr17-76497920; COSMIC: COSV67754477; COSMIC: COSV67754477;