Genetic Variant EAF2:p.Gln221Lys (chr3-121872713-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018456.6(EAF2):c.661C>A(p.Gln221Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0000034 ( 0 hom. )

Consequence

EAF2
NM_018456.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.61

Publications

0 publications found

Variant links:

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]

EAF2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12510246).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018456.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EAF2	NM_018456.6	MANE Select	c.661C>A	p.Gln221Lys	missense	Exon 5 of 6	NP_060926.2
	EAF2	NM_001320041.2		c.271C>A	p.Gln91Lys	missense	Exon 4 of 5	NP_001306970.1	Q96CJ1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EAF2	ENST00000273668.7	TSL:1 MANE Select	c.661C>A	p.Gln221Lys	missense	Exon 5 of 6	ENSP00000273668.2	Q96CJ1-1
EAF2	ENST00000490434.5	TSL:1	n.*317C>A		non_coding_transcript_exon	Exon 4 of 5	ENSP00000418374.1	F8WCI9
EAF2	ENST00000490434.5	TSL:1	n.*317C>A		3_prime_UTR	Exon 4 of 5	ENSP00000418374.1	F8WCI9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460934

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726786

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.00

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39606

South Asian (SAS)

AF:

0.00

AC:

AN:

86208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111438

Other (OTH)

AF:

0.0000497

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.13

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.66

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.49

M_CAP

Benign

0.0041

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

3.6

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.61

REVEL

Benign

0.064

Sift

Benign

0.17

Sift4G

Benign

0.90

Polyphen

0.0

Vest4

0.23

MutPred

0.28

Gain of methylation at Q221 (P = 0.0017)

MVP

0.11

MPC

0.13

ClinPred

0.065

GERP RS

2.9

Varity_R

0.085

gMVP

0.13

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over