chr8-142750353-C-T

Variant names:

• chr8-142750353-C-T
• NM_205545.3:c.308G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_205545.3(LYPD2):​c.308G>A​(p.Gly103Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G103R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: LYPD2 NM_205545.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0760

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a lipid_moiety_binding_region GPI-anchor amidated glycine (size 0) in uniprot entity LYPD2_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1523292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYPD2	NM_205545.3	c.308G>A	p.Gly103Glu	missense_variant	Exon 3 of 3	ENST00000359228.4	NP_991108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYPD2	ENST00000359228.4	c.308G>A	p.Gly103Glu	missense_variant	Exon 3 of 3	1	NM_205545.3	ENSP00000352163.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.308G>A (p.G103E) alteration is located in exon 3 (coding exon 3) of the LYPD2 gene. This alteration results from a G to A substitution at nucleotide position 308, causing the glycine (G) at amino acid position 103 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.91	P
Vest4		0.13
MutPred		0.44		Gain of solvent accessibility (P = 0.024);
MVP		0.38
MPC		0.51
ClinPred		0.98	D
GERP RS		2.5
Varity_R		0.30
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-143831771;