Variant 22-30098858-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_152510.4(HORMAD2):c.58G>C(p.Val20Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,608,456 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.015 ( 59 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 48 hom. )

Consequence

HORMAD2
NM_152510.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.407

Variant links:

Genes affected

HORMAD2 (HGNC:28383): (HORMA domain containing 2) Predicted to be involved in meiotic sister chromatid cohesion. Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

HORMAD2 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=0.001239866).

BP6

Variant 22-30098858-G-C is Benign according to our data. Variant chr22-30098858-G-C is described in ClinVar as [Benign]. Clinvar id is 788932.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HORMAD2	NM_152510.4 linkuse as main transcript	c.58G>C	p.Val20Leu	missense_variant	3/11	ENST00000336726.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HORMAD2	ENST00000336726.11 linkuse as main transcript	c.58G>C	p.Val20Leu	missense_variant	3/11	1	NM_152510.4	P1
HORMAD2	ENST00000403975.1 linkuse as main transcript	c.58G>C	p.Val20Leu	missense_variant	3/11	2		P1
HORMAD2	ENST00000491605.1 linkuse as main transcript	n.53G>C		non_coding_transcript_exon_variant	2/4	3
HORMAD2	ENST00000450612.5 linkuse as main transcript	c.58G>C	p.Val20Leu	missense_variant, NMD_transcript_variant	3/9	5

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2255

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0518

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00370

AC:

905

AN:

244694

Hom.:

AF XY:

0.00292

AC XY:

388

AN XY:

132746

show subpopulations

Gnomad AFR exome

AF:

0.0526

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000681

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000188

Gnomad OTH exome

AF:

0.00252

GnomAD4 exome

AF:

0.00154

AC:

2241

AN:

1456210

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

993

AN XY:

724330

show subpopulations

Gnomad4 AFR exome

AF:

0.0559

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000941

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000991

Gnomad4 OTH exome

AF:

0.00264

GnomAD4 genome

AF:

0.0148

AC:

2260

AN:

152246

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1078

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0518

Gnomad4 AMR

AF:

0.00491

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00230

Hom.:

Bravo

AF:

0.0170

ESP6500AA

AF:

0.0487

AC:

178

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.00459

AC:

554

Asia WGS

AF:

0.00347

AC:

AN:

3474

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

Invitae

Aug 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.1

DANN

Benign

0.87

DEOGEN2

Benign

0.0029

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.055

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.21

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.18

N;N

REVEL

Benign

0.048

Sift

Benign

0.51

T;T

Sift4G

Benign

0.43

T;T

Polyphen

0.0

B;B

Vest4

0.17

MVP

0.067

MPC

0.052

ClinPred

0.0021

GERP RS

-4.2

Varity_R

0.041

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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