22-30121738-C-T

Variant names:

• chr22-30121738-C-T
• NM_152510.4:c.517C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152510.4(HORMAD2):​c.517C>T​(p.Pro173Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HORMAD2 NM_152510.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.16
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HORMAD2	NM_152510.4	MANE Select	c.517C>T	p.Pro173Ser	missense	Exon 9 of 11	NP_689723.1	Q8N7B1
	HORMAD2	NM_001329457.2		c.517C>T	p.Pro173Ser	missense	Exon 10 of 12	NP_001316386.1	Q8N7B1
	HORMAD2	NM_001329458.2		c.253C>T	p.Pro85Ser	missense	Exon 8 of 10	NP_001316387.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HORMAD2	ENST00000336726.11	TSL:1 MANE Select	c.517C>T	p.Pro173Ser	missense	Exon 9 of 11	ENSP00000336984.6	Q8N7B1
	HORMAD2	ENST00000403975.1	TSL:2	c.517C>T	p.Pro173Ser	missense	Exon 9 of 11	ENSP00000385055.1	Q8N7B1
	HORMAD2	ENST00000862797.1		c.469C>T	p.Pro157Ser	missense	Exon 7 of 9	ENSP00000532856.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.2
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.27
Sift	Benign	0.030	D
Sift4G	Uncertain	0.014	D
Polyphen		0.85	P
Vest4		0.47
MutPred		0.72		Loss of loop (P = 0.2237)
MVP		0.53
MPC		0.31
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.50
gMVP		0.23
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

hg19: chr22-30517727;