rs7255045

chr19-12821455-G-A

Variant summary

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

The ENST00000589765.1(HOOK2):n.41+3723C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,732 control chromosomes in the GnomAD database, including 11,489 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 0.37 (11489 hom., cov: 31)
• Consequence: HOOK2 ENST00000589765.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 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
HOOK2	ENST00000589765.1	n.41+3723C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55827 AN: 151614 Hom.: 11472 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.368 AC: 55889 AN: 151732 Hom.: 11489 Cov.: 31 AF XY: 0.376 AC XY: 27839 AN XY: 74136

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.305

Alfa AF: 0.330 Hom.: 1096

Bravo AF: 0.370

Asia WGS AF: 0.495 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.43
Dann	Benign	0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7255045; hg19: chr19-12932269;