rs2412971

Variant names:

• chr22-30098382-G-A
• rs2412971
• NM_152510.4:c.52-470G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152510.4(HORMAD2):​c.52-470G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,950 control chromosomes in the GnomAD database, including 23,591 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 0.55 (23591 hom., cov: 31)
• Consequence: HORMAD2 NM_152510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.820
• Publications: 60 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

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.52-470G>A		intron	N/A	NP_689723.1	Q8N7B1
	HORMAD2	NM_001329457.2		c.52-470G>A		intron	N/A	NP_001316386.1	Q8N7B1
	HORMAD2	NM_001329458.2		c.-176-470G>A		intron	N/A	NP_001316387.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HORMAD2	ENST00000336726.11	TSL:1 MANE Select	c.52-470G>A		intron	N/A	ENSP00000336984.6	Q8N7B1
	HORMAD2	ENST00000403975.1	TSL:2	c.52-470G>A		intron	N/A	ENSP00000385055.1	Q8N7B1
	HORMAD2	ENST00000862797.1		c.52-470G>A		intron	N/A	ENSP00000532856.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82924 AN: 151832 Hom.: 23544 Cov.: 31

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.546 AC: 83037 AN: 151950 Hom.: 23591 Cov.: 31 AF XY: 0.552 AC XY: 40981 AN XY: 74264

African (AFR) AF: 0.694 AC: 28755 AN: 41452

American (AMR) AF: 0.597 AC: 9117 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1801 AN: 3468

East Asian (EAS) AF: 0.298 AC: 1539 AN: 5168

South Asian (SAS) AF: 0.609 AC: 2934 AN: 4818

European-Finnish (FIN) AF: 0.536 AC: 5640 AN: 10532

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31317 AN: 67920

Other (OTH) AF: 0.555 AC: 1175 AN: 2116

Alfa AF: 0.479 Hom.: 68852

Bravo AF: 0.550

Asia WGS AF: 0.508 AC: 1766 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.5
DANN	Benign	0.58
PhyloP100		0.82
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs2412971; hg19: chr22-30494371;