22-30108218-A-G

Position:

• chr22-30108218-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HORMAD2	NM_152510.4	c.295-3578A>G		intron_variant		ENST00000336726.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HORMAD2	ENST00000336726.11	c.295-3578A>G		intron_variant		1	NM_152510.4	P1
HORMAD2	ENST00000403975.1	c.295-3578A>G		intron_variant		2		P1
HORMAD2	ENST00000450612.5	c.258-3578A>G		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR AF: 0.0931

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.0920

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.261

Alfa AF: 0.244 Hom.: 3852

Bravo AF: 0.203

Asia WGS AF: 0.190 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.29
DANN	Benign	0.31

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: rs718772; hg19: chr22-30504207; COSMIC: COSV60901251; COSMIC: COSV60901251;