rs11077375

Positions:

• chr17-78495112-G-A
• chr17-78495112-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173628.4(DNAH17):​c.5904-15C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,585,328 control chromosomes in the GnomAD database, including 55,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4302 hom., cov: 34)
  • Exomes 𝑓: 0.26 (50734 hom.)
• Consequence: DNAH17 NM_173628.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.469

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-78495112-G-A is Benign according to our data. Variant chr17-78495112-G-A is described in ClinVar as [Benign]. Clinvar id is 402684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH17	NM_173628.4	c.5904-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000389840.7
DNAH17-AS1	NR_102401.1	n.769+915G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH17	ENST00000389840.7	c.5904-15C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_173628.4	P1
DNAH17-AS1	ENST00000591373.2	n.769+915G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.230 AC: 35045 AN: 152062 Hom.: 4296 Cov.: 34

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.253

GnomAD3 exomes AF: 0.276 AC: 59254 AN: 214656 Hom.: 8442 AF XY: 0.277 AC XY: 32269 AN XY: 116412

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.371

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.256

Gnomad SAS exome AF: 0.341

Gnomad FIN exome AF: 0.229

Gnomad NFE exome AF: 0.259

Gnomad OTH exome AF: 0.259

GnomAD4 exome AF: 0.263 AC: 376669 AN: 1433148 Hom.: 50734 Cov.: 37 AF XY: 0.265 AC XY: 188326 AN XY: 709688

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.360

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.264

Gnomad4 SAS exome AF: 0.340

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome AF: 0.230 AC: 35058 AN: 152180 Hom.: 4302 Cov.: 34 AF XY: 0.232 AC XY: 17236 AN XY: 74416

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.256

Alfa AF: 0.254 Hom.: 7439

Bravo AF: 0.232

Asia WGS AF: 0.290 AC: 1009 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.17
DANN	Benign	0.33

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: rs11077375; hg19: chr17-76491194;