chr7-86891765-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142749.3. 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
	ELAPOR2	NM_001142749.3	MANE Select	c.2989A>G	p.Lys997Glu	missense	Exon 21 of 22	NP_001136221.1	A8MWY0-1
	ELAPOR2	NM_001291990.1		c.2647A>G	p.Lys883Glu	missense	Exon 21 of 22	NP_001278919.1	B4E116
	ELAPOR2	NM_152748.4		c.2488A>G	p.Lys830Glu	missense	Exon 20 of 21	NP_689961.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAPOR2	ENST00000450689.7	TSL:5 MANE Select	c.2989A>G	p.Lys997Glu	missense	Exon 21 of 22	ENSP00000413445.2	A8MWY0-1
	ELAPOR2	ENST00000971399.1		c.3064A>G	p.Lys1022Glu	missense	Exon 22 of 23	ENSP00000641458.1
	ELAPOR2	ENST00000860453.1		c.2824A>G	p.Lys942Glu	missense	Exon 21 of 22	ENSP00000530512.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33356

American (AMR) AF: 0.00 AC: 0 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.00 AC: 0 AN: 86014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1110896

Other (OTH) AF: 0.00 AC: 0 AN: 60300

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000550

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.6
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.24
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.022	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
Mutation Taster		=32/68	disease causing

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: rs1788167763; hg19: chr7-86521081;