chr8-142750405-C-A

Variant names:

• chr8-142750405-C-A
• rs765580069
• NM_205545.3:c.256G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_205545.3(LYPD2):​c.256G>T​(p.Gly86Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G86S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LYPD2 NM_205545.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.818

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.256G>T	p.Gly86Cys	missense	Exon 3 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.256G>T	p.Gly86Cys	missense	Exon 3 of 3	ENSP00000352163.3	Q6UXB3
	ENSG00000253196	ENST00000839249.1		n.448+11921C>A		intron	N/A
	ENSG00000253196	ENST00000839250.1		n.296-8648C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1430814 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 708534

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32816

American (AMR) AF: 0.00 AC: 0 AN: 40484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25568

East Asian (EAS) AF: 0.00 AC: 0 AN: 37980

South Asian (SAS) AF: 0.00 AC: 0 AN: 81524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096644

Other (OTH) AF: 0.00 AC: 0 AN: 59226

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	0.047	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		1.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Pathogenic	0.66
Sift	Benign	0.052	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.79		Loss of sheet (P = 0.0315)
MVP		0.75
MPC		0.69
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.66
gMVP		0.93
Mutation Taster		=68/32	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: rs765580069; hg19: chr8-143831823;