19-12806286-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000639767.2(THSD8):c.*7-722G>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 325,972 control chromosomes in the GnomAD database, including 5,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2556 hom., cov: 32)
  • Exomes 𝑓: 0.19 (3417 hom.)
• Consequence: THSD8 ENST00000639767.2 intron, NMD_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.62

Genes affected

THSD8 (HGNC:53785): (thrombospondin type 1 domain containing 8)

HOOK2 (HGNC:19885): (hook microtubule tethering protein 2) Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment.[supplied by OMIM, Apr 2004]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-12806286-G-C is Benign according to our data. Variant chr19-12806286-G-C is described in ClinVar as [Benign]. Clinvar id is 1282221.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD8	ENST00000639767.2	c.*7-722G>C		intron_variant, NMD_transcript_variant		5
HOOK2	ENST00000589765.1	n.41+18892C>G		intron_variant, non_coding_transcript_variant		5
THSD8	ENST00000643364.1	n.396-99G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26535 AN: 152012 Hom.: 2543 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0770

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.194

GnomAD4 exome AF: 0.190 AC: 32944 AN: 173842 Hom.: 3417 AF XY: 0.189 AC XY: 17972 AN XY: 95086

Gnomad4 AFR exome AF: 0.0947

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.0631

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.175 AC: 26568 AN: 152130 Hom.: 2556 Cov.: 32 AF XY: 0.173 AC XY: 12866 AN XY: 74368

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.0772

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.202

Alfa AF: 0.181 Hom.: 339

Bravo AF: 0.177

Asia WGS AF: 0.167 AC: 581 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

Mar 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.29
Dann	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12461559; hg19: chr19-12917100;