22-30108218-A-G

Variant names:

• chr22-30108218-A-G
• rs718772
• NM_152510.4:c.295-3578A>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.295-3578A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 151,998 control chromosomes in the GnomAD database, including 3,894 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 0.21 (3894 hom., cov: 30)
• Consequence: HORMAD2 NM_152510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 10 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152510.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HORMAD2	NM_152510.4	MANE Select	c.295-3578A>G		intron	N/A	NP_689723.1
	HORMAD2	NM_001329457.2		c.295-3578A>G		intron	N/A	NP_001316386.1
	HORMAD2	NM_001329458.2		c.31-3578A>G		intron	N/A	NP_001316387.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HORMAD2	ENST00000336726.11	TSL:1 MANE Select	c.295-3578A>G		intron	N/A	ENSP00000336984.6
	HORMAD2	ENST00000403975.1	TSL:2	c.295-3578A>G		intron	N/A	ENSP00000385055.1
	HORMAD2	ENST00000450612.5	TSL:5	n.258-3578A>G		intron	N/A	ENSP00000393415.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32049 AN: 151880 Hom.: 3890 Cov.: 30

Gnomad AFR AF: 0.0933

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.0924

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.211 AC: 32066 AN: 151998 Hom.: 3894 Cov.: 30 AF XY: 0.214 AC XY: 15926 AN XY: 74302

African (AFR) AF: 0.0931 AC: 3862 AN: 41474

American (AMR) AF: 0.266 AC: 4061 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1095 AN: 3466

East Asian (EAS) AF: 0.0920 AC: 477 AN: 5182

South Asian (SAS) AF: 0.243 AC: 1173 AN: 4824

European-Finnish (FIN) AF: 0.300 AC: 3174 AN: 10566

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17324 AN: 67932

Other (OTH) AF: 0.261 AC: 551 AN: 2108

Alfa AF: 0.226 Hom.: 5413

Bravo AF: 0.203

Asia WGS AF: 0.190 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.29
DANN	Benign	0.31
PhyloP100		-1.0
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: rs718772; hg19: chr22-30504207; COSMIC: COSV60901251; COSMIC: COSV60901251;