rs7255045

Variant names:

• chr19-12821455-G-A
• rs7255045
• ENST00000589765.1:n.41+3723C>T

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 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
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOOK2	ENST00000589765.1	n.41+3723C>T		intron_variant	Intron 3 of 3	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;