Variant 22-30098918-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000336726.11(HORMAD2):c.118G>T(p.Ala40Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000589 in 1,613,144 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

HORMAD2
ENST00000336726.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.18

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HORMAD2	NM_152510.4 linkuse as main transcript	c.118G>T	p.Ala40Ser	missense_variant	3/11	ENST00000336726.11	NP_689723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
HORMAD2	ENST00000336726.11 linkuse as main transcript	c.118G>T	p.Ala40Ser	missense_variant	3/11	1	NM_152510.4	ENSP00000336984	P1
HORMAD2	ENST00000403975.1 linkuse as main transcript	c.118G>T	p.Ala40Ser	missense_variant	3/11	2		ENSP00000385055	P1
HORMAD2	ENST00000491605.1 linkuse as main transcript	n.113G>T		non_coding_transcript_exon_variant	2/4	3
HORMAD2	ENST00000450612.5 linkuse as main transcript	c.118G>T	p.Ala40Ser	missense_variant, NMD_transcript_variant	3/9	5		ENSP00000393415

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000924

AC:

AN:

248908

Hom.:

AF XY:

0.0000963

AC XY:

AN XY:

135036

show subpopulations

Gnomad AFR exome

AF:

0.0000647

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000623

AC:

AN:

1461112

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000702

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000670

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000368

AC:

ExAC

AF:

0.0000911

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2022

The c.118G>T (p.A40S) alteration is located in exon 3 (coding exon 2) of the HORMAD2 gene. This alteration results from a G to T substitution at nucleotide position 118, causing the alanine (A) at amino acid position 40 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

T;T

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

0.89

D;D

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.051

T;T

Polyphen

1.0

D;D

Vest4

0.47

MVP

0.38

MPC

0.33

ClinPred

0.52

GERP RS

5.4

Varity_R

0.62

gMVP

0.49

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