7-86891765-T-C

Variant names:

• chr7-86891765-T-C
• rs1788167763
• NM_001142749.3:c.2989A>G

Variant summary

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

The NM_001142749.3(ELAPOR2):​c.2989A>G​(p.Lys997Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,459,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: ELAPOR2 NM_001142749.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.60

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELAPOR2	NM_001142749.3	c.2989A>G	p.Lys997Glu	missense_variant	Exon 21 of 22	ENST00000450689.7	NP_001136221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELAPOR2	ENST00000450689.7	c.2989A>G	p.Lys997Glu	missense_variant	Exon 21 of 22	5	NM_001142749.3	ENSP00000413445.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1459928 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 726240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000198

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.0000550

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2989A>G (p.K997E) alteration is located in exon 21 (coding exon 21) of the KIAA1324L gene. This alteration results from a A to G substitution at nucleotide position 2989, causing the lysine (K) at amino acid position 997 to be replaced by a glutamic acid (E). 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	Uncertain	0.43
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T;T;.
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.75	D;D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.24
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.022	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.87
MutPred		0.21		Loss of ubiquitination at K997 (P = 0.0056);.;.;
MVP		0.34
MPC		0.76
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.39
gMVP		0.48

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: rs1788167763; hg19: chr7-86521081;