Genetic Variant NCR2:c.-23T>G (chr6-41335854-T-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004828.4(NCR2):c.-23T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00074 in 1,559,880 control chromosomes in the GnomAD database, including 8 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 0.0041 ( 5 hom., cov: 31)

Exomes 𝑓: 0.00037 ( 3 hom. )

Consequence

NCR2
NM_004828.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.58

Publications

15 publications found

Variant links:

Genes affected

NCR2 (HGNC:6732): (natural cytotoxicity triggering receptor 2) Predicted to enable signaling receptor activity. Predicted to be involved in cellular defense response and signal transduction. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. Predicted to be active in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

NCR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCR2	NM_004828.4 link	c.-23T>G		5_prime_UTR_variant	Exon 1 of 5	ENST00000373089.10	NP_004819.2	O95944-1
NCR2	XM_017011500.2 link	c.2T>G	p.Met1?	start_lost	Exon 1 of 5		XP_016866989.1
NCR2	NM_001199509.2 link	c.-23T>G		5_prime_UTR_variant	Exon 1 of 6		NP_001186438.1	O95944-2
NCR2	NM_001199510.2 link	c.-23T>G		5_prime_UTR_variant	Exon 1 of 6		NP_001186439.1	O95944-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NCR2	ENST00000373089.10 link	c.-23T>G	5_prime_UTR_variant	Exon 1 of 5	1	NM_004828.4	ENSP00000362181.5	O95944-1
NCR2	ENST00000373086.3 link	c.-23T>G	5_prime_UTR_variant	Exon 1 of 6	1		ENSP00000362178.3	O95944-2
NCR2	ENST00000373083.8 link	c.-23T>G	5_prime_UTR_variant	Exon 1 of 6	1		ENSP00000362175.4	O95944-3

Frequencies

GnomAD3 genomes

AF:

0.00415

AC:

631

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000993

AC:

169

AN:

170162

AF XY:

0.000624

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.000585

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000580

Gnomad OTH exome

AF:

0.000213

GnomAD4 exome

AF:

0.000373

AC:

525

AN:

1407862

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

224

AN XY:

695038

show subpopulations

African (AFR)

AF:

0.0142

AC:

456

AN:

32200

American (AMR)

AF:

0.000659

AC:

AN:

36444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25226

East Asian (EAS)

AF:

0.00

AC:

AN:

36726

South Asian (SAS)

AF:

0.0000125

AC:

AN:

79964

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49790

Middle Eastern (MID)

AF:

0.000350

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.00000923

AC:

AN:

1083378

Other (OTH)

AF:

0.000548

AC:

AN:

58424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

122

152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00414

AC:

630

AN:

152018

Hom.:

Cov.:

AF XY:

0.00393

AC XY:

292

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.0147

AC:

609

AN:

41442

American (AMR)

AF:

0.000785

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67972

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.0000309

Hom.:

42402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.4

(source)

DANN

Benign

0.39

PhyloP100

-1.6

PromoterAI

-0.030

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(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