7-86907686-C-T

Position:

• chr7-86907686-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142749.3(ELAPOR2):​c.2542G>A​(p.Val848Met) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ELAPOR2 NM_001142749.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

Genes affected

ELAPOR2 (HGNC:21945): (endosome-lysosome associated apoptosis and autophagy regulator family member 2) Predicted to enable BMP receptor binding activity. Predicted to be involved in negative regulation of nervous system development; positive regulation of BMP signaling pathway; and positive regulation of epidermis development. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09886804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAPOR2	NM_001142749.3	c.2542G>A	p.Val848Met	missense_variant	18/22	ENST00000450689.7	NP_001136221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAPOR2	ENST00000450689.7	c.2542G>A	p.Val848Met	missense_variant	18/22	5	NM_001142749.3	ENSP00000413445.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.2542G>A (p.V848M) alteration is located in exon 18 (coding exon 18) of the KIAA1324L gene. This alteration results from a G to A substitution at nucleotide position 2542, causing the valine (V) at amino acid position 848 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.0077	T;T;.
Eigen	Benign	-0.074
Eigen_PC	Benign	-0.056
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.099	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.020	N;N;N
REVEL	Benign	0.024
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.10	T;T;T
Polyphen		0.71	P;.;.
Vest4		0.073
MutPred		0.25		Loss of sheet (P = 0.0457);.;.;
MVP		0.16
MPC		0.49
ClinPred		0.79	D
GERP RS		3.0
Varity_R		0.045
gMVP		0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs1414001381; hg19: chr7-86537002;