chr2-218618813-G-A

Variant names:

• chr2-218618813-G-A
• rs140194396
• NM_032726.4:c.410+6G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_032726.4(PLCD4):​c.410+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,574,306 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (7 hom.)
• Consequence: PLCD4 NM_032726.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001821
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.654

Genes affected

PLCD4 (HGNC:9062): (phospholipase C delta 4) This gene encodes a member of the delta class of phospholipase C enzymes. Phospholipase C enzymes play a critical role in many cellular processes by hydrolyzing phosphatidylinositol 4,5-bisphosphate into two intracellular second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. Expression of this gene may be a marker for cancer. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-218618813-G-A is Benign according to our data. Variant chr2-218618813-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651882.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCD4	NM_032726.4	c.410+6G>A		splice_region_variant, intron_variant	Intron 4 of 15	ENST00000450993.7	NP_116115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCD4	ENST00000450993.7	c.410+6G>A		splice_region_variant, intron_variant	Intron 4 of 15	1	NM_032726.4	ENSP00000388631.2
PLCD4	ENST00000432688.5	c.410+6G>A		splice_region_variant, intron_variant	Intron 4 of 16	5		ENSP00000396185.1
PLCD4	ENST00000417849.5	c.410+6G>A		splice_region_variant, intron_variant	Intron 4 of 16	5		ENSP00000396942.1
PLCD4	ENST00000444453.5	n.*97+6G>A		splice_region_variant, intron_variant	Intron 4 of 4	4		ENSP00000415725.1
PLCD4	ENST00000446503.5	n.*97+6G>A		splice_region_variant, intron_variant	Intron 4 of 5	4		ENSP00000406040.1

Frequencies

GnomAD3 genomes AF: 0.00170 AC: 258 AN: 152186 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00179

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00245 AC: 454 AN: 185510 AF XY: 0.00264

Gnomad AFR exome AF: 0.0000945

Gnomad AMR exome AF: 0.000897

Gnomad ASJ exome AF: 0.00447

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00519

Gnomad NFE exome AF: 0.00198

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00173 AC: 2457 AN: 1422002 Hom.: 7 Cov.: 30 AF XY: 0.00188 AC XY: 1326 AN XY: 703622

African (AFR) AF: 0.000306 AC: 10 AN: 32670

American (AMR) AF: 0.000918 AC: 35 AN: 38114

Ashkenazi Jewish (ASJ) AF: 0.00369 AC: 94 AN: 25448

East Asian (EAS) AF: 0.00 AC: 0 AN: 37654

South Asian (SAS) AF: 0.00460 AC: 375 AN: 81434

European-Finnish (FIN) AF: 0.00484 AC: 246 AN: 50812

Middle Eastern (MID) AF: 0.00489 AC: 28 AN: 5722

European-Non Finnish (NFE) AF: 0.00143 AC: 1557 AN: 1091196

Other (OTH) AF: 0.00190 AC: 112 AN: 58952

GnomAD4 genome AF: 0.00168 AC: 256 AN: 152304 Hom.: 1 Cov.: 32 AF XY: 0.00195 AC XY: 145 AN XY: 74472

African (AFR) AF: 0.000337 AC: 14 AN: 41564

American (AMR) AF: 0.000850 AC: 13 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4826

European-Finnish (FIN) AF: 0.00452 AC: 48 AN: 10622

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00179 AC: 122 AN: 68026

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00199 Hom.: 1

Bravo AF: 0.00114

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PLCD4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.1
DANN	Benign	0.83
PhyloP100		-0.65
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
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

Publications

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Other links and lift over

dbSNP: rs140194396; hg19: chr2-219483536;