rs9620953

chr22-30150256-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152510.4(HORMAD2):c.820-25807C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 151,846 control chromosomes in the GnomAD database, including 3,724 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3724 hom., cov: 31)
• Consequence: HORMAD2 NM_152510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HORMAD2	NM_152510.4	c.820-25807C>T		intron_variant		ENST00000336726.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HORMAD2	ENST00000336726.11	c.820-25807C>T		intron_variant		1	NM_152510.4	P1
HORMAD2	ENST00000403975.1	c.820-25807C>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30871 AN: 151728 Hom.: 3728 Cov.: 31

Gnomad AFR AF: 0.0768

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.0646

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.203 AC: 30873 AN: 151846 Hom.: 3724 Cov.: 31 AF XY: 0.206 AC XY: 15301 AN XY: 74192

Gnomad4 AFR AF: 0.0767

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.0649

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.241

Alfa AF: 0.221 Hom.: 487

Bravo AF: 0.195

Asia WGS AF: 0.107 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.2
Dann	Benign	0.85

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

LitVar

Other links and lift over

dbSNP: rs9620953; hg19: chr22-30546245;