2-190516330-C-T

Variant names:

• chr2-190516330-C-T
• rs891251532
• NM_001142645.2:c.667G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142645.2(NEMP2):​c.667G>A​(p.Val223Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: NEMP2 NM_001142645.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.221
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051502287).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142645.2. 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
	NEMP2	NM_001142645.2	MANE Select	c.667G>A	p.Val223Ile	missense	Exon 6 of 9	NP_001136117.1	A6NFY4-1
	NEMP2	NR_136298.2		n.688G>A		non_coding_transcript_exon	Exon 6 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEMP2	ENST00000409150.8	TSL:2 MANE Select	c.667G>A	p.Val223Ile	missense	Exon 6 of 9	ENSP00000386292.3	A6NFY4-1
	NEMP2	ENST00000920104.1		c.667G>A	p.Val223Ile	missense	Exon 6 of 9	ENSP00000590163.1
	NEMP2	ENST00000343105.9	TSL:4	n.*202G>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000340087.5	F8VWJ7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399380 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 690198

African (AFR) AF: 0.00 AC: 0 AN: 31588

American (AMR) AF: 0.00 AC: 0 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35712

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078932

Other (OTH) AF: 0.00 AC: 0 AN: 58040

GnomAD4 genome Cov.: 32

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	Benign	0.078
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.20
DANN	Benign	0.38
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.22
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.039
Sift	Benign	1.0	T
Sift4G	Benign	0.55	T
Polyphen		0.043	B
Vest4		0.10
MutPred		0.54		Loss of catalytic residue at V223 (P = 8e-04)
MVP		0.055
ClinPred		0.018	T
GERP RS		-1.6
Varity_R		0.024
gMVP		0.045
Mutation Taster		=97/3	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: rs891251532; hg19: chr2-191381056;