19-12806286-G-C

Variant names:

• chr19-12806286-G-C
• rs12461559
• ENST00000589765.1:n.41+18892C>G

Variant summary

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

The ENST00000639767.2(THSD8):​n.*7-722G>C variant causes a intron 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.62

Genes affected

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]

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

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOOK2	ENST00000589765.1	n.41+18892C>G		intron_variant	Intron 3 of 3	5
THSD8	ENST00000639767.2	n.*7-722G>C		intron_variant	Intron 2 of 8	5		ENSP00000491410.2
THSD8	ENST00000643364.1	n.396-99G>C		intron_variant	Intron 2 of 2

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

Mar 23, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;