Variant 19-12766150-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_013312.3(HOOK2):c.1464C>G(p.His488Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,599,928 control chromosomes in the GnomAD database, including 112,472 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.29 ( 8122 hom., cov: 33)

Exomes 𝑓: 0.37 ( 104350 hom. )

Consequence

HOOK2
NM_013312.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.25

Variant links:

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]

HOOK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035521984).

BP6

Variant 19-12766150-G-C is Benign according to our data. Variant chr19-12766150-G-C is described in ClinVar as [Benign]. Clinvar id is 1225367.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOOK2	NM_013312.3 linkuse as main transcript	c.1464C>G	p.His488Gln	missense_variant	15/23	ENST00000397668.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOOK2	ENST00000397668.8 linkuse as main transcript	c.1464C>G	p.His488Gln	missense_variant	15/23	1	NM_013312.3	A1	Q96ED9-1

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44334

AN:

152048

Hom.:

8117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0766

Gnomad AMI

AF:

0.371

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.412

Gnomad OTH

AF:

0.323

GnomAD3 exomes

AF:

0.323

AC:

74070

AN:

229246

Hom.:

13330

AF XY:

0.327

AC XY:

41551

AN XY:

127088

show subpopulations

Gnomad AFR exome

AF:

0.0711

Gnomad AMR exome

AF:

0.244

Gnomad ASJ exome

AF:

0.456

Gnomad EAS exome

AF:

0.255

Gnomad SAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.409

Gnomad OTH exome

AF:

0.370

GnomAD4 exome

AF:

0.370

AC:

536196

AN:

1447762

Hom.:

104350

Cov.:

AF XY:

0.368

AC XY:

265085

AN XY:

720606

show subpopulations

Gnomad4 AFR exome

AF:

0.0662

Gnomad4 AMR exome

AF:

0.249

Gnomad4 ASJ exome

AF:

0.463

Gnomad4 EAS exome

AF:

0.231

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.372

Gnomad4 NFE exome

AF:

0.401

Gnomad4 OTH exome

AF:

0.351

GnomAD4 genome

AF:

0.291

AC:

44321

AN:

152166

Hom.:

8122

Cov.:

AF XY:

0.287

AC XY:

21342

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0765

Gnomad4 AMR

AF:

0.286

Gnomad4 ASJ

AF:

0.462

Gnomad4 EAS

AF:

0.246

Gnomad4 SAS

AF:

0.190

Gnomad4 FIN

AF:

0.365

Gnomad4 NFE

AF:

0.412

Gnomad4 OTH

AF:

0.320

Alfa

AF:

0.383

Hom.:

3596

Bravo

AF:

0.279

TwinsUK

AF:

0.404

AC:

1497

ALSPAC

AF:

0.400

AC:

1543

ESP6500AA

AF:

0.0836

AC:

323

ESP6500EA

AF:

0.394

AC:

3246

ExAC

AF:

0.320

AC:

38184

Asia WGS

AF:

0.169

AC:

587

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 29, 2020

This variant is associated with the following publications: (PMID: 32397755) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.0035

T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0036

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.17

N;N

MutationTaster

Benign

0.48

P;P

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.058

Sift

Benign

0.45

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.013

B;B

Vest4

0.050

MutPred

0.21

Gain of MoRF binding (P = 0.1143);Gain of MoRF binding (P = 0.1143);

MPC

0.25

ClinPred

0.0063

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.058

gMVP

0.055

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over