2-190534287-T-C

Position:

• chr2-190534287-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEMP2	NM_001142645.2	c.97+272A>G		intron_variant		ENST00000409150.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEMP2	ENST00000409150.8	c.97+272A>G		intron_variant		2	NM_001142645.2	P1

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

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.528

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.390

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.402

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.295

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

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.280

Alfa AF: 0.223 Hom.: 1782

Bravo AF: 0.309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.2
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs12622496; hg19: chr2-191399013;