17-78423999-G-A

Position:

• chr17-78423999-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_173628.4(DNAH17):​c.13296C>T​(p.Arg4432=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,614,034 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (12 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.699

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]

PGS1 (HGNC:30029): (phosphatidylglycerophosphate synthase 1) Predicted to enable CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity and calcium ion binding activity. Predicted to be involved in cardiolipin biosynthetic process and diacylglycerol metabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 17-78423999-G-A is Benign according to our data. Variant chr17-78423999-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648342.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.699 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00196 (298/152330) while in subpopulation NFE AF= 0.00323 (220/68026). AF 95% confidence interval is 0.00288. There are 1 homozygotes in gnomad4. There are 145 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.13296C>T	p.Arg4432=	synonymous_variant	81/81	ENST00000389840.7	NP_775899.3
PGS1	NM_024419.5	c.*11-62G>A		intron_variant		ENST00000262764.11	NP_077733.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.13296C>T	p.Arg4432=	synonymous_variant	81/81	5	NM_173628.4	ENSP00000374490	P1
PGS1	ENST00000262764.11	c.*11-62G>A		intron_variant		1	NM_024419.5	ENSP00000262764	P1

Frequencies

GnomAD3 genomes AF: 0.00196 AC: 298 AN: 152212 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00323

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00200 AC: 499 AN: 249746 Hom.: 1 AF XY: 0.00204 AC XY: 275 AN XY: 135124

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.000924

Gnomad NFE exome AF: 0.00355

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00333 AC: 4869 AN: 1461704 Hom.: 12 Cov.: 31 AF XY: 0.00318 AC XY: 2312 AN XY: 727136

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00130

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000441

Gnomad4 FIN exome AF: 0.00154

Gnomad4 NFE exome AF: 0.00404

Gnomad4 OTH exome AF: 0.00293

GnomAD4 genome AF: 0.00196 AC: 298 AN: 152330 Hom.: 1 Cov.: 33 AF XY: 0.00195 AC XY: 145 AN XY: 74474

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.00323

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00285 Hom.: 0

Bravo AF: 0.00188

EpiCase AF: 0.00240

EpiControl AF: 0.00320

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

DNAH17-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 25, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

DNAH17: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.9
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs117340568; hg19: chr17-76420080;