Genetic Variant HORMAD2:p.Pro298Ser (chr22-30176135-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152510.4(HORMAD2):c.892C>T(p.Pro298Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HORMAD2
NM_152510.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.109261364).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152510.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HORMAD2	NM_152510.4	MANE Select	c.892C>T	p.Pro298Ser	missense	Exon 11 of 11	NP_689723.1	Q8N7B1
HORMAD2	NM_001329457.2		c.892C>T	p.Pro298Ser	missense	Exon 12 of 12	NP_001316386.1	Q8N7B1
HORMAD2	NM_001329458.2		c.628C>T	p.Pro210Ser	missense	Exon 10 of 10	NP_001316387.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HORMAD2	ENST00000336726.11	TSL:1 MANE Select	c.892C>T	p.Pro298Ser	missense	Exon 11 of 11	ENSP00000336984.6	Q8N7B1
HORMAD2	ENST00000403975.1	TSL:2	c.892C>T	p.Pro298Ser	missense	Exon 11 of 11	ENSP00000385055.1	Q8N7B1
HORMAD2	ENST00000862797.1		c.844C>T	p.Pro282Ser	missense	Exon 9 of 9	ENSP00000532856.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459344

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726138

African (AFR)

AF:

0.00

AC:

AN:

33398

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110010

Other (OTH)

AF:

0.00

AC:

AN:

60276

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0065

Eigen

Benign

0.11

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.71

M_CAP

Benign

0.0099

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

1.3

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.1

REVEL

Benign

0.064

Sift

Pathogenic

0.0

Sift4G

Benign

0.25

Polyphen

0.80

Vest4

0.12

MutPred

0.33

Gain of phosphorylation at P298 (P = 0.0078)

MVP

0.29

MPC

0.069

ClinPred

0.38

GERP RS

3.7

Varity_R

0.35

gMVP

0.41

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over