17-78425144-T-TG

Position:

• chr17-78425144-T-TG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_173628.4(DNAH17):​c.13141+201_13141+202insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00631 in 581,342 control chromosomes in the GnomAD database, including 126 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (97 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (29 hom.)
• Consequence: DNAH17 NM_173628.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36

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 -10 ACMG points.

• BP6: Variant 17-78425144-T-TG is Benign according to our data. Variant chr17-78425144-T-TG is described in ClinVar as [Benign]. Clinvar id is 1241734.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.13141+201_13141+202insC		intron_variant		ENST00000389840.7	NP_775899.3
DNAH17	XM_011525416.3	c.13153+201_13153+202insC		intron_variant			XP_011523718.1
DNAH17	XM_024451013.2	c.13009+201_13009+202insC		intron_variant			XP_024306781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.13141+201_13141+202insC		intron_variant		5	NM_173628.4	ENSP00000374490	P1

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2596 AN: 152210 Hom.: 93 Cov.: 33

Gnomad AFR AF: 0.0588

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00241 AC: 1036 AN: 429014 Hom.: 29 Cov.: 5 AF XY: 0.00194 AC XY: 436 AN XY: 225252

Gnomad4 AFR exome AF: 0.0612

Gnomad4 AMR exome AF: 0.00442

Gnomad4 ASJ exome AF: 0.000155

Gnomad4 EAS exome AF: 0.0000344

Gnomad4 SAS exome AF: 0.000280

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000314

Gnomad4 OTH exome AF: 0.00530

GnomAD4 genome AF: 0.0173 AC: 2633 AN: 152328 Hom.: 97 Cov.: 33 AF XY: 0.0169 AC XY: 1257 AN XY: 74502

Gnomad4 AFR AF: 0.0594

Gnomad4 AMR AF: 0.00634

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.00255 Hom.: 1

Bravo AF: 0.0196

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs112942638; hg19: chr17-76421225;