chr2-232892987-A-G

Position:

• chr2-232892987-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_019850.3(NGEF):​c.1053T>C​(p.Ile351Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.952 in 1,613,308 control chromosomes in the GnomAD database, including 731,888 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 0.96 (70399 hom., cov: 33)
  • Exomes 𝑓: 0.95 (661489 hom.)
• Consequence: NGEF NM_019850.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387

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]

NGEF (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.387 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGEF	NM_019850.3	c.1053T>C	p.Ile351Ile	synonymous_variant	7/15	ENST00000264051.8	NP_062824.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGEF	ENST00000264051.8	c.1053T>C	p.Ile351Ile	synonymous_variant	7/15	1	NM_019850.3	ENSP00000264051.3
NGEF	ENST00000373552.8	c.777T>C	p.Ile259Ile	synonymous_variant	5/13	2		ENSP00000362653.4
NGEF	ENST00000416114.3	c.222T>C	p.Ile74Ile	synonymous_variant	3/6	3		ENSP00000401063.1
NGEF	ENST00000420650.2	n.430T>C		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.961 AC: 146233 AN: 152206 Hom.: 70341 Cov.: 33

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.967

GnomAD3 exomes AF: 0.949 AC: 237850 AN: 250664 Hom.: 112987 AF XY: 0.948 AC XY: 128609 AN XY: 135702

Gnomad AFR exome AF: 0.989

Gnomad AMR exome AF: 0.952

Gnomad ASJ exome AF: 0.992

Gnomad EAS exome AF: 0.883

Gnomad SAS exome AF: 0.923

Gnomad FIN exome AF: 0.947

Gnomad NFE exome AF: 0.956

Gnomad OTH exome AF: 0.950

GnomAD4 exome AF: 0.951 AC: 1389963 AN: 1460984 Hom.: 661489 Cov.: 49 AF XY: 0.951 AC XY: 690917 AN XY: 726738

Gnomad4 AFR exome AF: 0.992

Gnomad4 AMR exome AF: 0.950

Gnomad4 ASJ exome AF: 0.993

Gnomad4 EAS exome AF: 0.919

Gnomad4 SAS exome AF: 0.924

Gnomad4 FIN exome AF: 0.948

Gnomad4 NFE exome AF: 0.953

Gnomad4 OTH exome AF: 0.947

GnomAD4 genome AF: 0.961 AC: 146350 AN: 152324 Hom.: 70399 Cov.: 33 AF XY: 0.960 AC XY: 71464 AN XY: 74476

Gnomad4 AFR AF: 0.990

Gnomad4 AMR AF: 0.952

Gnomad4 ASJ AF: 0.989

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.913

Gnomad4 FIN AF: 0.950

Gnomad4 NFE AF: 0.956

Gnomad4 OTH AF: 0.967

Alfa AF: 0.959 Hom.: 44862

Bravo AF: 0.964

Asia WGS AF: 0.906 AC: 3154 AN: 3478

EpiCase AF: 0.960

EpiControl AF: 0.959

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.6
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs895432; hg19: chr2-233757697;