rs2412973

Positions:

• chr22-30133642-C-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• 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/exons	MANE	Protein	UniProt
HORMAD2	NM_152510.4	c.819+11428C>A		intron_variant		ENST00000336726.11	NP_689723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HORMAD2	ENST00000336726.11	c.819+11428C>A		intron_variant		1	NM_152510.4	ENSP00000336984	P1
HORMAD2	ENST00000403975.1	c.819+11428C>A		intron_variant		2		ENSP00000385055	P1

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

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.551

Alfa AF: 0.449 Hom.: 24196

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

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: rs2412973; hg19: chr22-30529631;