rs72925845

Positions:

• chr17-78443279-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173628.4(DNAH17):​c.11528+1325C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 152,222 control chromosomes in the GnomAD database, including 616 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.087 (616 hom., cov: 32)
• Consequence: DNAH17 NM_173628.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH17	NM_173628.4	c.11528+1325C>T		intron_variant		ENST00000389840.7
DNAH17	XM_011525416.3	c.11528+1325C>T		intron_variant
DNAH17	XM_024451013.2	c.11384+1325C>T		intron_variant
DNAH17	XM_047436981.1	c.11528+1325C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH17	ENST00000389840.7	c.11528+1325C>T		intron_variant		5	NM_173628.4	P1
DNAH17	ENST00000591369.5	c.3130+1325C>T		intron_variant, NMD_transcript_variant		5
DNAH17	ENST00000586052.5	n.4813+1325C>T		intron_variant, non_coding_transcript_variant		5
DNAH17	ENST00000590227.5	n.1202+1325C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0867 AC: 13181 AN: 152104 Hom.: 615 Cov.: 32

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0522

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.102

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0866 AC: 13180 AN: 152222 Hom.: 616 Cov.: 32 AF XY: 0.0840 AC XY: 6249 AN XY: 74436

Gnomad4 AFR AF: 0.0519

Gnomad4 AMR AF: 0.0725

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0520

Gnomad4 SAS AF: 0.0733

Gnomad4 FIN AF: 0.0694

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0927 Hom.: 81

Bravo AF: 0.0863

Asia WGS AF: 0.0550 AC: 193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.83

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: rs72925845; hg19: chr17-76439361;