chr1-23792743-G-A

Variant names:

• chr1-23792743-G-A
• rs140351723
• NM_007260.3:c.61G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_007260.3(LYPLA2):​c.61G>A​(p.Glu21Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,612,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E21Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: LYPLA2 NM_007260.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.01
• Publications: 2 publications found

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]

ENSG00000289835 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29677653).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007260.3. 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
	LYPLA2	NM_007260.3	MANE Select	c.61G>A	p.Glu21Lys	missense	Exon 2 of 10	NP_009191.1	O95372

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYPLA2	ENST00000374514.8	TSL:1 MANE Select	c.61G>A	p.Glu21Lys	missense	Exon 2 of 10	ENSP00000363638.3	O95372
	LYPLA2	ENST00000905312.1		c.61G>A	p.Glu21Lys	missense	Exon 2 of 10	ENSP00000575370.1
	LYPLA2	ENST00000905307.1		c.61G>A	p.Glu21Lys	missense	Exon 2 of 10	ENSP00000575366.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000959 AC: 14 AN: 1460320 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 726502

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

Middle Eastern (MID) AF: 0.000212 AC: 1 AN: 4716

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111880

Other (OTH) AF: 0.00 AC: 0 AN: 60270

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

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

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.054
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		6.0
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.20
Sift	Benign	0.79	T
Sift4G	Benign	0.88	T
Polyphen		0.022	B
Vest4		0.72
MutPred		0.58		Gain of methylation at E21 (P = 0.0062)
MVP		0.17
MPC		0.87
ClinPred		0.81	D
GERP RS		4.1
Varity_R		0.55
gMVP		0.92
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs140351723; hg19: chr1-24119233;