rs2412973

Variant names:

• chr22-30133642-C-A
• rs2412973
• NM_152510.4:c.819+11428C>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.819+11428C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 148,508 control chromosomes in the GnomAD database, including 22,206 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 0.54 (22206 hom., cov: 28)
• Consequence: HORMAD2 NM_152510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 56 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HORMAD2	NM_152510.4	c.819+11428C>A		intron_variant	Intron 10 of 10	ENST00000336726.11	NP_689723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HORMAD2	ENST00000336726.11	c.819+11428C>A		intron_variant	Intron 10 of 10	1	NM_152510.4	ENSP00000336984.6
HORMAD2	ENST00000403975.1	c.819+11428C>A		intron_variant	Intron 10 of 10	2		ENSP00000385055.1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 79992 AN: 148462 Hom.: 22189 Cov.: 28

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.610

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.539 AC: 80039 AN: 148508 Hom.: 22206 Cov.: 28 AF XY: 0.544 AC XY: 39398 AN XY: 72444

African (AFR) AF: 0.680 AC: 27442 AN: 40332

American (AMR) AF: 0.591 AC: 8830 AN: 14934

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1794 AN: 3460

East Asian (EAS) AF: 0.303 AC: 1557 AN: 5140

South Asian (SAS) AF: 0.603 AC: 2826 AN: 4690

European-Finnish (FIN) AF: 0.522 AC: 5066 AN: 9700

Middle Eastern (MID) AF: 0.615 AC: 176 AN: 286

European-Non Finnish (NFE) AF: 0.457 AC: 30633 AN: 66996

Other (OTH) AF: 0.551 AC: 1140 AN: 2068

Alfa AF: 0.469 Hom.: 60740

Bravo AF: 0.541

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.71
PhyloP100		-1.2
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: rs2412973; hg19: chr22-30529631;