chr17-31318769-T-A

Position:

• chr17-31318769-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014210.4(EVI2A):​c.245A>T​(p.His82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 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)
• Consequence: EVI2A NM_014210.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.48

Genes affected

EVI2A (HGNC:3499): (ecotropic viral integration site 2A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000265118 (HGNC:):

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054007232).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVI2A	NM_014210.4	c.245A>T	p.His82Leu	missense_variant	2/2	ENST00000462804.3	NP_055025.2
NF1	NM_001042492.3	c.4836-7051T>A		intron_variant		ENST00000358273.9	NP_001035957.1
EVI2A	NM_001003927.3	c.314A>T	p.His105Leu	missense_variant	3/3		NP_001003927.1
NF1	NM_000267.3	c.4773-7051T>A		intron_variant			NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVI2A	ENST00000462804.3	c.245A>T	p.His82Leu	missense_variant	2/2	1	NM_014210.4	ENSP00000420557.3
ENSG00000265118	ENST00000578584.5	c.17A>T	p.His6Leu	missense_variant	1/3	2		ENSP00000463981.2
NF1	ENST00000358273.9	c.4836-7051T>A		intron_variant		1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2024

The c.314A>T (p.H105L) alteration is located in exon 3 (coding exon 2) of the EVI2A gene. This alteration results from a A to T substitution at nucleotide position 314, causing the histidine (H) at amino acid position 105 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.41
DANN	Benign	0.53
DEOGEN2	Benign	0.046	.;T;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.35	T;.;T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.054	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.3	.;L;.;L
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.43	.;N;N;.
REVEL	Benign	0.039
Sift	Benign	0.68	.;T;T;.
Sift4G	Benign	0.59	T;T;T;T
Polyphen		0.0	.;B;B;B
Vest4		0.12
MutPred		0.43		.;Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);
MVP		0.25
MPC		0.029
ClinPred		0.038	T
GERP RS		-6.7
Varity_R		0.055
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr17-29645787;