rs1409240185

Variant names:

• chr22-30098952-G-A
• NM_152510.4:c.152G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-30098952-G-A
• chr22-30098952-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152510.4(HORMAD2):​c.152G>A​(p.Gly51Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G51V) has been classified 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.938

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HORMAD2	NM_152510.4	c.152G>A	p.Gly51Asp	missense_variant	Exon 3 of 11	ENST00000336726.11	NP_689723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HORMAD2	ENST00000336726.11	c.152G>A	p.Gly51Asp	missense_variant	Exon 3 of 11	1	NM_152510.4	ENSP00000336984.6
HORMAD2	ENST00000403975.1	c.152G>A	p.Gly51Asp	missense_variant	Exon 3 of 11	2		ENSP00000385055.1
HORMAD2	ENST00000450612.5	n.152G>A		non_coding_transcript_exon_variant	Exon 3 of 9	5		ENSP00000393415.1
HORMAD2	ENST00000491605.1	n.147G>A		non_coding_transcript_exon_variant	Exon 2 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460534 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726568

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	.;D
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Uncertain	0.35
Sift	Benign	0.076	T;T
Sift4G	Uncertain	0.022	D;D
Polyphen		0.98	D;D
Vest4		0.87
MutPred		0.81		Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);
MVP		0.48
MPC		0.38
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.51
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-30494941;