1-23793916-A-C

Position:

• chr1-23793916-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007260.3(LYPLA2):​c.281A>C​(p.Lys94Thr) variant causes a missense change. 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LYPLA2 NM_007260.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.59

Genes affected

LYPLA2 (HGNC:6738): (lysophospholipase 2) Lysophospholipases are enzymes that act on biological membranes to regulate the multifunctional lysophospholipids. There are alternatively spliced transcript variants described for this gene but the full length nature is not known yet. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25525564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYPLA2	NM_007260.3	c.281A>C	p.Lys94Thr	missense_variant	6/10	ENST00000374514.8	NP_009191.1
LYPLA2	XM_005245728.6	c.317A>C	p.Lys106Thr	missense_variant	6/10		XP_005245785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYPLA2	ENST00000374514.8	c.281A>C	p.Lys94Thr	missense_variant	6/10	1	NM_007260.3	ENSP00000363638.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.281A>C (p.K94T) alteration is located in exon 6 (coding exon 5) of the LYPLA2 gene. This alteration results from a A to C substitution at nucleotide position 281, causing the lysine (K) at amino acid position 94 to be replaced by a threonine (T). 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	0.29
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	T;T;T;T;T;T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;.;.;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.1	N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.40	T;T;T;T;T;T
Sift4G	Benign	0.55	T;T;T;T;T;T
Polyphen		0.10	B;.;P;P;.;.
Vest4		0.72
MutPred		0.46		Loss of ubiquitination at K94 (P = 0.0155);.;Loss of ubiquitination at K94 (P = 0.0155);Loss of ubiquitination at K94 (P = 0.0155);Loss of ubiquitination at K94 (P = 0.0155);.;
MVP		0.12
MPC		1.6
ClinPred		0.83	D
GERP RS		5.3
Varity_R		0.32
gMVP		0.83

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-24120406;