rs955573345

Variant names:

• chr15-51724902-C-T
• rs955573345
• NM_153374.3:c.493G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153374.3(LYSMD2):​c.493G>A​(p.Asp165Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LYSMD2 NM_153374.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78
• Publications: 0 publications found

Genes affected

LYSMD2 (HGNC:28571): (LysM domain containing 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07947931).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153374.3. 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
	LYSMD2	NM_153374.3	MANE Select	c.493G>A	p.Asp165Asn	missense	Exon 2 of 3	NP_699205.1	Q8IV50-1
	LYSMD2	NM_001143917.2		c.220G>A	p.Asp74Asn	missense	Exon 2 of 3	NP_001137389.1	Q8IV50-2
	LYSMD2	NM_001363969.2		c.220G>A	p.Asp74Asn	missense	Exon 2 of 3	NP_001350898.1	Q8IV50-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYSMD2	ENST00000267838.7	TSL:1 MANE Select	c.493G>A	p.Asp165Asn	missense	Exon 2 of 3	ENSP00000267838.3	Q8IV50-1
	LYSMD2	ENST00000454181.6	TSL:1	c.220G>A	p.Asp74Asn	missense	Exon 2 of 3	ENSP00000410424.2	Q8IV50-2
	LYSMD2	ENST00000875743.1		c.484G>A	p.Asp162Asn	missense	Exon 2 of 3	ENSP00000545802.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251360 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461808 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.069
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.049
Sift	Benign	0.34	T
Sift4G	Benign	0.47	T
Polyphen		0.039	B
Vest4		0.045
MutPred		0.20		Gain of glycosylation at P161 (P = 0.1875)
MVP		0.35
MPC		0.14
ClinPred		0.076	T
GERP RS		1.4
Varity_R		0.039
gMVP		0.22

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: rs955573345; hg19: chr15-52017099;