7-86891860-A-G

Position:

• chr7-86891860-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001142749.3(ELAPOR2):​c.2894T>C​(p.Met965Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELAPOR2 NM_001142749.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.87

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]

ELAPOR2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.805

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAPOR2	NM_001142749.3	c.2894T>C	p.Met965Thr	missense_variant	21/22	ENST00000450689.7	NP_001136221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAPOR2	ENST00000450689.7	c.2894T>C	p.Met965Thr	missense_variant	21/22	5	NM_001142749.3	ENSP00000413445.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

Dec 03, 2024

The c.2894T>C (p.M965T) alteration is located in exon 21 (coding exon 21) of the KIAA1324L gene. This alteration results from a T to C substitution at nucleotide position 2894, causing the methionine (M) at amino acid position 965 to be replaced by a threonine (T). 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	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;T;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.81	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.84
MutPred		0.39		Gain of glycosylation at M965 (P = 0.0225);.;.;
MVP		0.56
MPC		0.85
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.56
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-86521176;