22-30196080-T-C

Position:

• chr22-30196080-T-C

Variant summary

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

The XM_011529914.3(HORMAD2):​c.820-10905T>C 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: HORMAD2 XM_011529914.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HORMAD2	XM_011529914.3	c.820-10905T>C		intron_variant			XP_011528216.1
HORMAD2	XM_017028622.2	c.820-10905T>C		intron_variant			XP_016884111.1
HORMAD2	XM_047441154.1	c.820-10905T>C		intron_variant			XP_047297110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000225676	ENST00000432360.2	n.149-3850A>G		intron_variant		3

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

Gnomad4 AFR AF: 0.901

Gnomad4 AMR AF: 0.951

Gnomad4 ASJ AF: 0.947

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.990

Gnomad4 FIN AF: 0.906

Gnomad4 NFE AF: 0.916

Gnomad4 OTH AF: 0.930

Alfa AF: 0.923 Hom.: 76984

Bravo AF: 0.921

Asia WGS AF: 0.987 AC: 3433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2412980; hg19: chr22-30592069;