7-86893051-G-A

Variant names:

• chr7-86893051-G-A
• rs749291023
• NM_001142749.3:c.2735C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142749.3(ELAPOR2):​c.2735C>T​(p.Ser912Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000703 in 1,421,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S912Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ELAPOR2 NM_001142749.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77
• Publications: 6 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18948567).

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.2735C>T	p.Ser912Phe	missense	Exon 20 of 22	NP_001136221.1	A8MWY0-1
	ELAPOR2	NM_001291990.1		c.2393C>T	p.Ser798Phe	missense	Exon 20 of 22	NP_001278919.1	B4E116
	ELAPOR2	NM_152748.4		c.2234C>T	p.Ser745Phe	missense	Exon 19 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.2735C>T	p.Ser912Phe	missense	Exon 20 of 22	ENSP00000413445.2	A8MWY0-1
	ELAPOR2	ENST00000971399.1		c.2810C>T	p.Ser937Phe	missense	Exon 21 of 23	ENSP00000641458.1
	ELAPOR2	ENST00000860453.1		c.2570C>T	p.Ser857Phe	missense	Exon 20 of 22	ENSP00000530512.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 215134 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1421820 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 706522

African (AFR) AF: 0.0000334 AC: 1 AN: 29908

American (AMR) AF: 0.00 AC: 0 AN: 36516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25372

East Asian (EAS) AF: 0.00 AC: 0 AN: 36540

South Asian (SAS) AF: 0.00 AC: 0 AN: 78866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097150

Other (OTH) AF: 0.00 AC: 0 AN: 58766

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.8
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.12
Sift	Uncertain	0.025	D
Sift4G	Benign	0.085	T
Polyphen		0.025	B
Vest4		0.25
MutPred		0.43		Gain of sheet (P = 0.0344)
MVP		0.32
MPC		0.25
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.28
gMVP		0.72
Mutation Taster		=67/33	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: rs749291023; hg19: chr7-86522367; COSMIC: COSV99789101; COSMIC: COSV99789101;