2-190534568-C-G

Position:

• chr2-190534568-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001142645.2(NEMP2):​c.88G>C​(p.Ala30Pro) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEMP2 NM_001142645.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15

Genes affected

NEMP2 (HGNC:33700): (nuclear envelope integral membrane protein 2) Predicted to be located in nuclear inner membrane. Predicted to be integral component of membrane. Predicted to be active in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28141734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEMP2	NM_001142645.2	c.88G>C	p.Ala30Pro	missense_variant	1/9	ENST00000409150.8	NP_001136117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEMP2	ENST00000409150.8	c.88G>C	p.Ala30Pro	missense_variant	1/9	2	NM_001142645.2	ENSP00000386292	P1
NEMP2	ENST00000343105.9	c.88G>C	p.Ala30Pro	missense_variant, NMD_transcript_variant	1/6	4		ENSP00000340087

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1249706 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 612974

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

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

Apr 19, 2023

The c.88G>C (p.A30P) alteration is located in exon 1 (coding exon 1) of the NEMP2 gene. This alteration results from a G to C substitution at nucleotide position 88, causing the alanine (A) at amino acid position 30 to be replaced by a proline (P). 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	0.17
BayesDel_addAF	Benign	-0.0037	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.36	T
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.12
Sift	Benign	0.089	T
Sift4G	Benign	0.075	T
Polyphen		0.64	P
Vest4		0.43
MutPred		0.47		Gain of loop (P = 3e-04);
MVP		0.23
ClinPred		0.28	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.15
gMVP		0.40

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: chr2-191399294;