rs17042882

Positions:

• chr3-16930384-C-A
• chr3-16930384-C-G
• chr3-16930384-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001144382.2(PLCL2):​c.327+45018C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 152,206 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.015 (24 hom., cov: 32)
• Consequence: PLCL2 NM_001144382.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277

Genes affected

PLCL2 (HGNC:9064): (phospholipase C like 2) Enables GABA receptor binding activity. Predicted to be involved in negative regulation of cold-induced thermogenesis and phosphatidylinositol-mediated signaling. Predicted to act upstream of or within several processes, including B cell activation; gamma-aminobutyric acid signaling pathway; and negative regulation of B cell receptor signaling pathway. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0152 (2318/152206) while in subpopulation NFE AF= 0.0269 (1827/68006). AF 95% confidence interval is 0.0258. There are 24 homozygotes in gnomad4. There are 1077 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2318 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCL2	NM_001144382.2	c.327+45018C>A		intron_variant		ENST00000615277.5	NP_001137854.1
PLCL2	XM_047447799.1	c.-6480C>A		5_prime_UTR_variant	1/7		XP_047303755.1
PLCL2	XM_006713073.4	c.12+30700C>A		intron_variant			XP_006713136.1
PLCL2	XM_017006025.2	c.-155-7171C>A		intron_variant			XP_016861514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCL2	ENST00000615277.5	c.327+45018C>A		intron_variant		1	NM_001144382.2	ENSP00000478458
PLCL2	ENST00000460467.1	n.439-79290C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2321 AN: 152090 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.00488

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00664

Gnomad FIN AF: 0.00624

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0100

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0152 AC: 2318 AN: 152206 Hom.: 24 Cov.: 32 AF XY: 0.0145 AC XY: 1077 AN XY: 74442

Gnomad4 AFR AF: 0.00486

Gnomad4 AMR AF: 0.00804

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00644

Gnomad4 FIN AF: 0.00624

Gnomad4 NFE AF: 0.0269

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.0169 Hom.: 12

Bravo AF: 0.0142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.6
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17042882; hg19: chr3-16971876;