rs2412971

chr22-30098382-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HORMAD2	NM_152510.4	c.52-470G>A		intron_variant		ENST00000336726.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HORMAD2	ENST00000336726.11	c.52-470G>A		intron_variant		1	NM_152510.4	P1
HORMAD2	ENST00000403975.1	c.52-470G>A		intron_variant		2		P1
HORMAD2	ENST00000450612.5	c.52-470G>A		intron_variant, NMD_transcript_variant		5
HORMAD2	ENST00000491605.1	n.47-470G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.555

Alfa AF: 0.470 Hom.: 29289

Bravo AF: 0.550

Asia WGS AF: 0.508 AC: 1766 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	4.5
Dann	Benign	0.58

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: rs2412971; hg19: chr22-30494371;