3-121854718-G-T

Variant names:

• chr3-121854718-G-T
• rs1708687759
• NM_018456.6:c.233G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018456.6(EAF2):​c.233G>T​(p.Gly78Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,407,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: EAF2 NM_018456.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.89

Genes affected

EAF2 (HGNC:23115): (ELL associated factor 2) Enables transcription elongation regulator activity. Involved in positive regulation of transcription by RNA polymerase II and regulation of transcription elongation from RNA polymerase II promoter. Part of transcription elongation factor complex. Biomarker of prostate cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.931

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EAF2	NM_018456.6	c.233G>T	p.Gly78Val	missense_variant	Exon 3 of 6	ENST00000273668.7	NP_060926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EAF2	ENST00000273668.7	c.233G>T	p.Gly78Val	missense_variant	Exon 3 of 6	1	NM_018456.6	ENSP00000273668.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000284 AC: 4 AN: 1407076 Hom.: 0 Cov.: 30 AF XY: 0.00000572 AC XY: 4 AN XY: 699630

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: 0.00000365

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.233G>T (p.G78V) alteration is located in exon 3 (coding exon 3) of the EAF2 gene. This alteration results from a G to T substitution at nucleotide position 233, causing the glycine (G) at amino acid position 78 to be replaced by a valine (V). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D;D
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Pathogenic	3.0	M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-8.1	D;D
REVEL	Pathogenic	0.79
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.98
MutPred		0.76		Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);
MVP		0.45
MPC		0.56
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.95
gMVP		0.85

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: rs1708687759; hg19: chr3-121573565;