17-31319014-G-T

Variant names:

• chr17-31319014-G-T
• NM_014210.4:c.-1C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001003927.3(EVI2A):​c.69C>A​(p.Ser23Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,439,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EVI2A NM_001003927.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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]

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]

ENSG00000265118 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09094399).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVI2A	NM_014210.4	c.-1C>A		5_prime_UTR_variant	Exon 2 of 2	ENST00000462804.3	NP_055025.2
NF1	NM_001042492.3	c.4836-6806G>T		intron_variant	Intron 36 of 57	ENST00000358273.9	NP_001035957.1
EVI2A	NM_001003927.3	c.69C>A	p.Ser23Arg	missense_variant	Exon 3 of 3		NP_001003927.1
NF1	NM_000267.3	c.4773-6806G>T		intron_variant	Intron 35 of 56		NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVI2A	ENST00000462804.3	c.-1C>A		5_prime_UTR_variant	Exon 2 of 2	1	NM_014210.4	ENSP00000420557.3
NF1	ENST00000358273.9	c.4836-6806G>T		intron_variant	Intron 36 of 57	1	NM_001042492.3	ENSP00000351015.4
ENSG00000265118	ENST00000578584.5	c.-229C>A		upstream_gene_variant		2		ENSP00000463981.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1439174 Hom.: 0 Cov.: 39 AF XY: 0.00000140 AC XY: 1 AN XY: 715178

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: 9.05e-7

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.5
DANN	Benign	0.80
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.99	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.014
Sift	Benign	0.068	T
Polyphen		0.044	B
Vest4		0.19
MutPred		0.26		Gain of catalytic residue at S23 (P = 0.012);
MVP		0.17
MPC		0.032
ClinPred		0.19	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
gMVP		0.22

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.

Other links and lift over

hg19: chr17-29646032;