rs5753025

Positions:

• chr22-30146168-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152510.4(HORMAD2):​c.819+23954T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,112 control chromosomes in the GnomAD database, including 38,654 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 0.70 (38654 hom., cov: 32)
• Consequence: HORMAD2 NM_152510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HORMAD2	NM_152510.4	c.819+23954T>C		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+23954T>C		intron_variant		1	NM_152510.4	ENSP00000336984.6
HORMAD2	ENST00000403975.1	c.819+23954T>C		intron_variant		2		ENSP00000385055.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106820 AN: 151994 Hom.: 38583 Cov.: 32

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.703 AC: 106961 AN: 152112 Hom.: 38654 Cov.: 32 AF XY: 0.710 AC XY: 52802 AN XY: 74342

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.715

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.868

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.685

Alfa AF: 0.688 Hom.: 5368

Bravo AF: 0.701

Asia WGS AF: 0.691 AC: 2403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.59

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: rs5753025; hg19: chr22-30542157;