chr22-30146168-T-C

Variant names:

• chr22-30146168-T-C
• rs5753025
• NM_152510.4:c.819+23954T>C

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+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
• Publications: 6 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=-0.94).
• 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 rank	MANE	Protein	UniProt
HORMAD2	NM_152510.4	c.819+23954T>C		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+23954T>C		intron_variant	Intron 10 of 10	1	NM_152510.4	ENSP00000336984.6
HORMAD2	ENST00000403975.1	c.819+23954T>C		intron_variant	Intron 10 of 10	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

African (AFR) AF: 0.855 AC: 35471 AN: 41506

American (AMR) AF: 0.715 AC: 10931 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2165 AN: 3472

East Asian (EAS) AF: 0.426 AC: 2194 AN: 5156

South Asian (SAS) AF: 0.868 AC: 4184 AN: 4822

European-Finnish (FIN) AF: 0.693 AC: 7320 AN: 10566

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42397 AN: 67992

Other (OTH) AF: 0.685 AC: 1446 AN: 2112

Alfa AF: 0.694 Hom.: 5654

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
PhyloP100		-1.3
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: rs5753025; hg19: chr22-30542157;