chr3-121872683-A-T

Position:

• chr3-121872683-A-T

Variant summary

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

The NM_018456.6(EAF2):​c.631A>T​(p.Asn211Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: EAF2 NM_018456.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11020404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EAF2	NM_018456.6	c.631A>T	p.Asn211Tyr	missense_variant	5/6	ENST00000273668.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EAF2	ENST00000273668.7	c.631A>T	p.Asn211Tyr	missense_variant	5/6	1	NM_018456.6	P1
EAF2	ENST00000490434.5	c.*287A>T		3_prime_UTR_variant, NMD_transcript_variant	4/5	1
EAF2	ENST00000451944.2	c.631A>T	p.Asn211Tyr	missense_variant	5/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461014 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 726822

Gnomad4 AFR exome AF: 0.000239

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: 0.00

Gnomad4 OTH exome AF: 0.0000994

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.631A>T (p.N211Y) alteration is located in exon 5 (coding exon 5) of the EAF2 gene. This alteration results from a A to T substitution at nucleotide position 631, causing the asparagine (N) at amino acid position 211 to be replaced by a tyrosine (Y). 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	Benign	0.079
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.067
Sift	Benign	0.041	D;D
Sift4G	Uncertain	0.042	D;D
Polyphen		0.76	P;.
Vest4		0.24
MutPred		0.16		Gain of phosphorylation at N211 (P = 0.0168);Gain of phosphorylation at N211 (P = 0.0168);
MVP		0.081
MPC		0.19
ClinPred		0.23	T
GERP RS		3.3
Varity_R		0.047
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1475808486; hg19: chr3-121591530;