rs2841280

Variant names:

• chr14-104927219-G-A
• rs2841280
• NM_138790.5:c.79G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-104927219-G-A
• chr14-104927219-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138790.5(PLD4):​c.79G>A​(p.Glu27Lys) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLD4 NM_138790.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 32 publications found

Genes affected

PLD4 (HGNC:23792): (phospholipase D family member 4) Predicted to enable single-stranded DNA 5'-3' exodeoxyribonuclease activity. Predicted to be involved in hematopoietic progenitor cell differentiation; phagocytosis; and regulation of cytokine production involved in inflammatory response. Predicted to be located in early endosome and endoplasmic reticulum membrane. Predicted to be active in several cellular components, including endoplasmic reticulum; phagocytic vesicle; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042895406).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138790.5. 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
	PLD4	NM_138790.5	MANE Select	c.79G>A	p.Glu27Lys	missense	Exon 2 of 11	NP_620145.2	Q96BZ4
	PLD4	NM_001308174.2		c.100G>A	p.Glu34Lys	missense	Exon 2 of 11	NP_001295103.1	F5H2B5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD4	ENST00000392593.9	TSL:1 MANE Select	c.79G>A	p.Glu27Lys	missense	Exon 2 of 11	ENSP00000376372.5	Q96BZ4
	PLD4	ENST00000540372.5	TSL:2	c.100G>A	p.Glu34Lys	missense	Exon 2 of 11	ENSP00000438677.1	F5H2B5
	PLD4	ENST00000862746.1		c.79G>A	p.Glu27Lys	missense	Exon 2 of 11	ENSP00000532805.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1398638 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 690444

African (AFR) AF: 0.00 AC: 0 AN: 31792

American (AMR) AF: 0.00 AC: 0 AN: 35046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24964

East Asian (EAS) AF: 0.00 AC: 0 AN: 36192

South Asian (SAS) AF: 0.00 AC: 0 AN: 79108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079692

Other (OTH) AF: 0.00 AC: 0 AN: 57856

GnomAD4 genome Cov.: 33

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.8
DANN	Benign	0.48
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.2
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.024
Sift	Benign	0.86	T
Sift4G	Benign	0.91	T
Polyphen		0.0	B
Vest4		0.089
MutPred		0.37		Gain of catalytic residue at Q39 (P = 0.0077)
MVP		0.18
MPC		0.096
ClinPred		0.068	T
GERP RS		1.2
Varity_R		0.065
gMVP		0.26
Mutation Taster		=99/1	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: rs2841280; hg19: chr14-105393556;