22-30196080-T-C

Variant names:

• chr22-30196080-T-C
• rs2412980
• XM_011529914.3:c.820-10905T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000432360.3(ENSG00000225676):​n.209-3850A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 152,272 control chromosomes in the GnomAD database, including 64,546 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 0.92 (64546 hom., cov: 33)
• Consequence: ENSG00000225676 ENST00000432360.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364
• Publications: 19 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]

ENSG00000225676 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000432360.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC105372988	NR_188588.1		n.148-3850A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000225676	ENST00000432360.3	TSL:3	n.209-3850A>G		intron	N/A
	ENSG00000225676	ENST00000760101.1		n.148-3850A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.920 AC: 140009 AN: 152154 Hom.: 64502 Cov.: 33

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.990

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.929

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

GnomAD4 genome AF: 0.920 AC: 140110 AN: 152272 Hom.: 64546 Cov.: 33 AF XY: 0.922 AC XY: 68603 AN XY: 74444

African (AFR) AF: 0.901 AC: 37433 AN: 41554

American (AMR) AF: 0.951 AC: 14555 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 3286 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5184

South Asian (SAS) AF: 0.990 AC: 4775 AN: 4824

European-Finnish (FIN) AF: 0.906 AC: 9598 AN: 10592

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.916 AC: 62284 AN: 68018

Other (OTH) AF: 0.930 AC: 1967 AN: 2114

Alfa AF: 0.923 Hom.: 128137

Bravo AF: 0.921

Asia WGS AF: 0.987 AC: 3433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.70
PhyloP100		0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2412980; hg19: chr22-30592069;