rs8962

Positions:

• chr2-190506923-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142645.2(NEMP2):​c.*2266C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,102 control chromosomes in the GnomAD database, including 1,839 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 0.15 (1838 hom., cov: 32)
  • Exomes 𝑓: 0.27 (1 hom.)
• Consequence: NEMP2 NM_001142645.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301

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]

MFSD6 (HGNC:24711): (major facilitator superfamily domain containing 6) Predicted to enable MHC class I protein binding activity and MHC class I receptor activity. Predicted to be involved in antigen processing and presentation of exogenous peptide antigen via MHC class I. Located in membrane. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEMP2	NM_001142645.2	c.*2266C>T		3_prime_UTR_variant	9/9	ENST00000409150.8	NP_001136117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEMP2	ENST00000409150.8	c.*2266C>T		3_prime_UTR_variant	9/9	2	NM_001142645.2	ENSP00000386292	P1
MFSD6	ENST00000412482.1	c.*184+1802G>A		intron_variant, NMD_transcript_variant		3		ENSP00000404511

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22231 AN: 151962 Hom.: 1837 Cov.: 32

Gnomad AFR AF: 0.0750

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.273 AC: 6 AN: 22 Hom.: 1 Cov.: 0 AF XY: 0.143 AC XY: 2 AN XY: 14

Gnomad4 NFE exome AF: 0.0833

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.146 AC: 22233 AN: 152080 Hom.: 1838 Cov.: 32 AF XY: 0.144 AC XY: 10673 AN XY: 74350

Gnomad4 AFR AF: 0.0750

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.161

Alfa AF: 0.161 Hom.: 681

Bravo AF: 0.144

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.7
DANN	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs8962; hg19: chr2-191371649;