22-30090837-A-G

Variant names:

• chr22-30090837-A-G
• rs2412970
• NM_152510.4:c.-37-3079A>G

Variant summary

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

The NM_152510.4(HORMAD2):​c.-37-3079A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,108 control chromosomes in the GnomAD database, including 23,651 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 (23651 hom., cov: 32)
• Consequence: HORMAD2 NM_152510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 44 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HORMAD2	NM_152510.4	c.-37-3079A>G		intron_variant	Intron 1 of 10	ENST00000336726.11	NP_689723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HORMAD2	ENST00000336726.11	c.-37-3079A>G		intron_variant	Intron 1 of 10	1	NM_152510.4	ENSP00000336984.6
HORMAD2	ENST00000403975.1	c.-37-3079A>G		intron_variant	Intron 1 of 10	2		ENSP00000385055.1
HORMAD2	ENST00000450612.5	n.-37-3079A>G		intron_variant	Intron 1 of 8	5		ENSP00000393415.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 83050 AN: 151986 Hom.: 23601 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.520

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: 0.547 AC: 83168 AN: 152108 Hom.: 23651 Cov.: 32 AF XY: 0.552 AC XY: 41042 AN XY: 74352

African (AFR) AF: 0.695 AC: 28822 AN: 41490

American (AMR) AF: 0.597 AC: 9128 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1801 AN: 3466

East Asian (EAS) AF: 0.298 AC: 1546 AN: 5180

South Asian (SAS) AF: 0.609 AC: 2938 AN: 4824

European-Finnish (FIN) AF: 0.536 AC: 5663 AN: 10562

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

European-Non Finnish (NFE) AF: 0.461 AC: 31339 AN: 67980

Other (OTH) AF: 0.556 AC: 1175 AN: 2114

Alfa AF: 0.487 Hom.: 36977

Bravo AF: 0.550

Asia WGS AF: 0.507 AC: 1763 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.74
PhyloP100		-1.5
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: rs2412970; hg19: chr22-30486826;