8-142752447-C-G

Variant names:

• chr8-142752447-C-G
• rs369898532
• NM_205545.3:c.5G>C

Variant summary

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

The NM_205545.3(LYPD2):​c.5G>C​(p.Arg2Pro) 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 1,461,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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: LYPD2 NM_205545.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -7.73
• Publications: 3 publications found

Genes affected

LYPD2 (HGNC:25215): (LY6/PLAUR domain containing 2) Predicted to be located in extracellular region and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000253196 (HGNC:58427):

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=0.0567739).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205545.3. 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
	LYPD2	NM_205545.3	MANE Select	c.5G>C	p.Arg2Pro	missense	Exon 1 of 3	NP_991108.1	F1T0L0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYPD2	ENST00000359228.4	TSL:1 MANE Select	c.5G>C	p.Arg2Pro	missense	Exon 1 of 3	ENSP00000352163.3	Q6UXB3
	ENSG00000253196	ENST00000839249.1		n.449-10789C>G		intron	N/A
	ENSG00000253196	ENST00000839250.1		n.296-6606C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461084 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726876

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

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111772

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 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	0.073
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.0020
DANN	Benign	0.67
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	L
PhyloP100		-7.7
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.16
Sift	Benign	0.12	T
Sift4G	Benign	0.29	T
Polyphen		0.0080	B
Vest4		0.12
MutPred		0.43		Loss of MoRF binding (P = 2e-04)
MVP		0.088
MPC		0.26
ClinPred		0.39	T
GERP RS		-8.6
PromoterAI		0.17	Neutral
Varity_R		0.19
gMVP		0.53
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs369898532; hg19: chr8-143833865;