chr2-190534287-T-C

Variant names:

• chr2-190534287-T-C
• rs12622496
• NM_001142645.2:c.97+272A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142645.2(NEMP2):​c.97+272A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,162,904 control chromosomes in the GnomAD database, including 42,629 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (7482 hom., cov: 33)
  • Exomes 𝑓: 0.26 (35147 hom.)
• Consequence: NEMP2 NM_001142645.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEMP2	NM_001142645.2	MANE Select	c.97+272A>G		intron	N/A	NP_001136117.1
	NEMP2	NR_136298.2		n.164+272A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEMP2	ENST00000409150.8	TSL:2 MANE Select	c.97+272A>G		intron	N/A	ENSP00000386292.3
	NEMP2	ENST00000414176.5	TSL:2	n.-386A>G		non_coding_transcript_exon	Exon 1 of 7	ENSP00000404283.1
	NEMP2	ENST00000492292.1	TSL:5	n.42A>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45131 AN: 152082 Hom.: 7458 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.260 AC: 262346 AN: 1010704 Hom.: 35147 Cov.: 19 AF XY: 0.259 AC XY: 123141 AN XY: 475322

African (AFR) AF: 0.291 AC: 6033 AN: 20716

American (AMR) AF: 0.528 AC: 3318 AN: 6284

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 3308 AN: 11604

East Asian (EAS) AF: 0.390 AC: 7794 AN: 19978

South Asian (SAS) AF: 0.229 AC: 4302 AN: 18766

European-Finnish (FIN) AF: 0.402 AC: 6743 AN: 16792

Middle Eastern (MID) AF: 0.229 AC: 590 AN: 2572

European-Non Finnish (NFE) AF: 0.250 AC: 218693 AN: 874828

Other (OTH) AF: 0.295 AC: 11565 AN: 39164

GnomAD4 genome AF: 0.297 AC: 45191 AN: 152200 Hom.: 7482 Cov.: 33 AF XY: 0.309 AC XY: 22981 AN XY: 74404

African (AFR) AF: 0.289 AC: 12014 AN: 41542

American (AMR) AF: 0.458 AC: 7002 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 973 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2385 AN: 5182

South Asian (SAS) AF: 0.222 AC: 1072 AN: 4828

European-Finnish (FIN) AF: 0.408 AC: 4311 AN: 10578

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16569 AN: 67982

Other (OTH) AF: 0.280 AC: 591 AN: 2112

Alfa AF: 0.227 Hom.: 2056

Bravo AF: 0.309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.2
DANN	Benign	0.56
PhyloP100		-0.47
PromoterAI		0.19	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12622496; hg19: chr2-191399013;