chr2-190517573-C-T

Variant names:

• chr2-190517573-C-T
• rs1690605570
• NM_001142645.2:c.559G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001142645.2(NEMP2):​c.559G>A​(p.Val187Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,252 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NEMP2 NM_001142645.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.796
• 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=0.07744482).
• BP6: Variant 2-190517573-C-T is Benign according to our data. Variant chr2-190517573-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3193526.Status of the report is criteria_provided_single_submitter, 1 stars.

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.559G>A	p.Val187Ile	missense	Exon 5 of 9	NP_001136117.1	A6NFY4-1
	NEMP2	NR_136298.2		n.626G>A		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEMP2	ENST00000409150.8	TSL:2 MANE Select	c.559G>A	p.Val187Ile	missense	Exon 5 of 9	ENSP00000386292.3	A6NFY4-1
	NEMP2	ENST00000920104.1		c.559G>A	p.Val187Ile	missense	Exon 5 of 9	ENSP00000590163.1
	NEMP2	ENST00000343105.9	TSL:4	n.*140G>A		non_coding_transcript_exon	Exon 5 of 6	ENSP00000340087.5	F8VWJ7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398252 Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2 AN XY: 689676

African (AFR) AF: 0.00 AC: 0 AN: 31506

American (AMR) AF: 0.00 AC: 0 AN: 35400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25142

East Asian (EAS) AF: 0.00 AC: 0 AN: 35560

South Asian (SAS) AF: 0.00 AC: 0 AN: 78930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49454

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

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078486

Other (OTH) AF: 0.00 AC: 0 AN: 58074

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.071
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.2
DANN	Benign	0.53
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.80
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.070
Sift	Benign	1.0	T
Sift4G	Benign	0.50	T
Polyphen		0.19	B
Vest4		0.082
MutPred		0.58		Gain of helix (P = 0.1736)
MVP		0.11
ClinPred		0.056	T
GERP RS		-5.4
Varity_R		0.014
gMVP		0.12
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1690605570; hg19: chr2-191382299;