chr2-232892987-A-T

Variant names:

• chr2-232892987-A-T
• rs895432
• NM_019850.3:c.1053T>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_019850.3(NGEF):​c.1053T>A​(p.Ile351Ile) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NGEF NM_019850.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387
• Publications: 17 publications found

Genes affected

NGEF (HGNC:7807): (neuronal guanine nucleotide exchange factor) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in several processes, including activation of GTPase activity; ephrin receptor signaling pathway; and negative regulation of dendritic spine morphogenesis. Predicted to be located in cytosol. Predicted to be active in glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.087).
• BP7: Synonymous conserved (PhyloP=0.387 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019850.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGEF	NM_019850.3	MANE Select	c.1053T>A	p.Ile351Ile	synonymous	Exon 7 of 15	NP_062824.2
	NGEF	NM_001114090.2		c.777T>A	p.Ile259Ile	synonymous	Exon 5 of 13	NP_001107562.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGEF	ENST00000264051.8	TSL:1 MANE Select	c.1053T>A	p.Ile351Ile	synonymous	Exon 7 of 15	ENSP00000264051.3
	NGEF	ENST00000373552.8	TSL:2	c.777T>A	p.Ile259Ile	synonymous	Exon 5 of 13	ENSP00000362653.4
	NGEF	ENST00000416114.3	TSL:3	c.222T>A	p.Ile74Ile	synonymous	Exon 3 of 6	ENSP00000401063.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 59965

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.5
DANN	Benign	0.72
PhyloP100		0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs895432; hg19: chr2-233757697;