Genetic Variant NM_001142645.2:c.*2266C>T (chr2-190506923-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.301

Publications

2 publications found

Variant links:

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]

NEMP2 links:

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]

MFSD6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NEMP2	NM_001142645.2 link	c.*2266C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000409150.8	NP_001136117.1	A6NFY4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEMP2	ENST00000409150.8 link	c.*2266C>T		3_prime_UTR_variant	Exon 9 of 9	2	NM_001142645.2	ENSP00000386292.3		A6NFY4-1
MFSD6	ENST00000412482.1 link	n.*184+1802G>A		intron_variant	Intron 3 of 3	3		ENSP00000404511.1		H7C284

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22231

AN:

151962

Hom.:

1837

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.143

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0833

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.146

AC:

22233

AN:

152080

Hom.:

1838

Cov.:

AF XY:

0.144

AC XY:

10673

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0750

AC:

3110

AN:

41494

American (AMR)

AF:

0.140

AC:

2146

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

851

AN:

3464

East Asian (EAS)

AF:

0.147

AC:

760

AN:

5164

South Asian (SAS)

AF:

0.162

AC:

783

AN:

4824

European-Finnish (FIN)

AF:

0.115

AC:

1215

AN:

10566

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.188

AC:

12797

AN:

67966

Other (OTH)

AF:

0.161

AC:

339

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

947

1893

2840

3786

4733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.164

Hom.:

882

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

(source)

DANN

Benign

0.48

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over