Variant 19-12763569-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_013312.3(HOOK2):c.1969G>A(p.Glu657Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00868 in 1,614,220 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 77 hom. )

Consequence

HOOK2
NM_013312.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.11

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008423775).

BP6

Variant 19-12763569-C-T is Benign according to our data. Variant chr19-12763569-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 774525.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOOK2	NM_013312.3 linkuse as main transcript	c.1969G>A	p.Glu657Lys	missense_variant	22/23	ENST00000397668.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOOK2	ENST00000397668.8 linkuse as main transcript	c.1969G>A	p.Glu657Lys	missense_variant	22/23	1	NM_013312.3	A1	Q96ED9-1
HOOK2	ENST00000264827.9 linkuse as main transcript	c.1963G>A	p.Glu655Lys	missense_variant	21/22	1		P4	Q96ED9-2
HOOK2	ENST00000589915.1 linkuse as main transcript	n.154G>A		non_coding_transcript_exon_variant	1/2	2
HOOK2	ENST00000678590.1 linkuse as main transcript	c.*1490G>A		3_prime_UTR_variant, NMD_transcript_variant	22/23

Frequencies

GnomAD3 genomes

AF:

0.00563

AC:

857

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.00671

GnomAD3 exomes

AF:

0.00559

AC:

1402

AN:

250890

Hom.:

AF XY:

0.00554

AC XY:

752

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.00131

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00304

Gnomad FIN exome

AF:

0.00259

Gnomad NFE exome

AF:

0.00955

Gnomad OTH exome

AF:

0.00670

GnomAD4 exome

AF:

0.00900

AC:

13154

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00864

AC XY:

6284

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00239

Gnomad4 ASJ exome

AF:

0.00195

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00327

Gnomad4 FIN exome

AF:

0.00243

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.00816

GnomAD4 genome

AF:

0.00562

AC:

856

AN:

152332

Hom.:

Cov.:

AF XY:

0.00487

AC XY:

363

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00868

Hom.:

Bravo

AF:

0.00545

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00942

AC:

ExAC

AF:

0.00544

AC:

660

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00845

EpiControl

AF:

0.0100

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.065

T;.

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.0084

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

0.98

D;D

Vest4

0.50

MVP

0.28

MPC

0.93

ClinPred

0.040

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.44

gMVP

0.32

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