chr2-233002956-A-G

Variant names:

• chr2-233002956-A-G
• rs6720354
• NM_019850.3:c.-75+10112T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019850.3(NGEF):​c.-75+10112T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,994 control chromosomes in the GnomAD database, including 21,751 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 0.52 (21751 hom., cov: 31)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271
• Publications: 2 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]

ENSG00000222001 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGEF	NM_019850.3	c.-75+10112T>C		intron_variant	Intron 1 of 14	ENST00000264051.8	NP_062824.2
NGEF	XM_011510923.4	c.-75+9843T>C		intron_variant	Intron 1 of 14		XP_011509225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGEF	ENST00000264051.8	c.-75+10112T>C		intron_variant	Intron 1 of 14	1	NM_019850.3	ENSP00000264051.3
ENSG00000222001	ENST00000783807.1	n.68-9799A>G		intron_variant	Intron 1 of 3
ENSG00000222001	ENST00000783808.1	n.27+4655A>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79618 AN: 151876 Hom.: 21723 Cov.: 31

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.494

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.524 AC: 79688 AN: 151994 Hom.: 21751 Cov.: 31 AF XY: 0.528 AC XY: 39202 AN XY: 74302

African (AFR) AF: 0.585 AC: 24247 AN: 41452

American (AMR) AF: 0.519 AC: 7937 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1358 AN: 3466

East Asian (EAS) AF: 0.921 AC: 4746 AN: 5152

South Asian (SAS) AF: 0.660 AC: 3182 AN: 4824

European-Finnish (FIN) AF: 0.469 AC: 4967 AN: 10590

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31429 AN: 67914

Other (OTH) AF: 0.500 AC: 1056 AN: 2112

Alfa AF: 0.354 Hom.: 1090

Bravo AF: 0.533

Asia WGS AF: 0.754 AC: 2619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.84
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs6720354; hg19: chr2-233867666;