2-175941013-C-A

Variant names:

• chr2-175941013-C-A
• rs760528892
• ENST00000544803.5:c.774G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001305009.1(LNPK):​c.774G>T​(p.Ser258Ser) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S258S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LNPK NM_001305009.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 0 publications found

Genes affected

LNPK (HGNC:21610): (lunapark, ER junction formation factor) Enables identical protein binding activity. Involved in endoplasmic reticulum tubular network maintenance and positive regulation of endoplasmic reticulum tubular network organization. Located in endoplasmic reticulum tubular network membrane and nucleoplasm. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

LNPK Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-1.36 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305009.1. 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
	LNPK	NM_030650.3	MANE Select	c.707-1356G>T		intron	N/A	NP_085153.1	Q9C0E8-1
	LNPK	NM_001305009.1		c.774G>T	p.Ser258Ser	synonymous	Exon 10 of 14	NP_001291938.1	Q9C0E8-4
	LNPK	NM_001305008.1		c.905-1356G>T		intron	N/A	NP_001291937.1	Q9C0E8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNPK	ENST00000544803.5	TSL:1	c.774G>T	p.Ser258Ser	synonymous	Exon 10 of 14	ENSP00000440905.1	Q9C0E8-4
	LNPK	ENST00000272748.9	TSL:1 MANE Select	c.707-1356G>T		intron	N/A	ENSP00000272748.4	Q9C0E8-1
	LNPK	ENST00000409660.5	TSL:1	c.338-1356G>T		intron	N/A	ENSP00000386237.1	Q9C0E8-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.22
DANN	Benign	0.37
PhyloP100		-1.4
Mutation Taster		=100/0	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: rs760528892; hg19: chr2-176805741;