chr8-142750345-C-A

Variant names:

• chr8-142750345-C-A
• rs587612897
• NM_205545.3:c.316G>T

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.316G>T​(p.Ala106Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,405,158 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. 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. A106T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: LYPD2 NM_205545.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• 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: 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=0.032291263).

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.316G>T	p.Ala106Ser	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.316G>T	p.Ala106Ser	missense	Exon 3 of 3	ENSP00000352163.3	Q6UXB3
	ENSG00000253196	ENST00000839249.1		n.448+11861C>A		intron	N/A
	ENSG00000253196	ENST00000839250.1		n.296-8708C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1405158 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 693642

African (AFR) AF: 0.00 AC: 0 AN: 31936

American (AMR) AF: 0.00 AC: 0 AN: 36498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25248

East Asian (EAS) AF: 0.00 AC: 0 AN: 36214

South Asian (SAS) AF: 0.00 AC: 0 AN: 79574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1082592

Other (OTH) AF: 0.00 AC: 0 AN: 58230

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.0040
DANN	Benign	0.16
DEOGEN2	Benign	0.00087	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.20	N
PhyloP100		-1.7
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.036
Sift	Benign	0.82	T
Sift4G	Benign	1.0	T
Polyphen		0.022	B
Vest4		0.097
MutPred		0.27		Gain of disorder (P = 0.0333)
MVP		0.040
MPC		0.14
ClinPred		0.070	T
GERP RS		-3.8
Varity_R		0.063
gMVP		0.70
Mutation Taster		=99/1	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: rs587612897; hg19: chr8-143831763;