dbSNP rs139395003: EVI2B:p.Asp311Tyr (chr17-31304679-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006495.4(EVI2B):c.931G>T(p.Asp311Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EVI2B
NM_006495.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.06

Variant links:

Genes affected

EVI2B (HGNC:3500): (ecotropic viral integration site 2B) Involved in positive regulation of granulocyte differentiation. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVI2B links:

NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]

NF1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2679399).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVI2B	NM_006495.4 link	c.931G>T	p.Asp311Tyr	missense_variant	Exon 2 of 2	ENST00000330927.5	NP_006486.3	P34910-1Q9BRW1
NF1	NM_001042492.3 link	c.4836-21141C>A		intron_variant	Intron 36 of 57	ENST00000358273.9	NP_001035957.1	P21359-1
NF1	NM_000267.3 link	c.4773-21141C>A		intron_variant	Intron 35 of 56		NP_000258.1	P21359-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVI2B	ENST00000330927.5 link	c.931G>T	p.Asp311Tyr	missense_variant	Exon 2 of 2	1	NM_006495.4	ENSP00000333779.4		P34910-1
NF1	ENST00000358273.9 link	c.4836-21141C>A		intron_variant	Intron 36 of 57	1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

-0.092

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.57

.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

L;L

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-4.4

D;.

REVEL

Benign

0.15

Sift

Uncertain

0.021

D;.

Sift4G

Uncertain

0.017

D;D

Polyphen

0.99

D;D

Vest4

0.31

MVP

0.69

MPC

0.28

ClinPred

0.91

GERP RS

4.7

Varity_R

0.22

gMVP

0.34

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over