chr22-30122008-A-T

Variant names:

• chr22-30122008-A-T
• rs757118057
• NM_152510.4:c.613A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152510.4(HORMAD2):​c.613A>T​(p.Asn205Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000626 in 1,612,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: HORMAD2 NM_152510.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.016736805).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HORMAD2	NM_152510.4	MANE Select	c.613A>T	p.Asn205Tyr	missense	Exon 10 of 11	NP_689723.1	Q8N7B1
	HORMAD2	NM_001329457.2		c.613A>T	p.Asn205Tyr	missense	Exon 11 of 12	NP_001316386.1	Q8N7B1
	HORMAD2	NM_001329458.2		c.349A>T	p.Asn117Tyr	missense	Exon 9 of 10	NP_001316387.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HORMAD2	ENST00000336726.11	TSL:1 MANE Select	c.613A>T	p.Asn205Tyr	missense	Exon 10 of 11	ENSP00000336984.6	Q8N7B1
	HORMAD2	ENST00000403975.1	TSL:2	c.613A>T	p.Asn205Tyr	missense	Exon 10 of 11	ENSP00000385055.1	Q8N7B1
	HORMAD2	ENST00000862797.1		c.565A>T	p.Asn189Tyr	missense	Exon 8 of 9	ENSP00000532856.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000146 AC: 36 AN: 246504 AF XY: 0.000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00351

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000623 AC: 91 AN: 1460490 Hom.: 0 Cov.: 31 AF XY: 0.0000661 AC XY: 48 AN XY: 726402

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.00310 AC: 81 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111320

Other (OTH) AF: 0.0000994 AC: 6 AN: 60346

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000270 Hom.: 0

Bravo AF: 0.0000680

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000828 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.5
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.087
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.027	D
Polyphen		0.85	P
Vest4		0.33
MVP		0.23
MPC		0.31
ClinPred		0.20	T
GERP RS		3.6
Varity_R		0.25
gMVP		0.28
Mutation Taster		=75/25	polymorphism

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: rs757118057; hg19: chr22-30517997;