Variant summary

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

The NM_021008.4(DEAF1):c.80C>A(p.Ala27Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A27V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DEAF1
NM_021008.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.759

Publications

1 publications found

Variant links:

Genes affected

DEAF1 (HGNC:14677): (DEAF1 transcription factor) This gene encodes a zinc finger domain-containing protein that functions as a regulator of transcription. The encoded proteins binds to its own promoter as well as to that of several target genes. Activity of this protein is important in the regulation of embryonic development. Mutations in this gene have been found in individuals with autosomal dominant cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

DEAF1 links:

EPS8L2 (HGNC:21296): (EPS8 signaling adaptor L2) This gene encodes a member of the EPS8 gene family. The encoded protein, like other members of the family, is thought to link growth factor stimulation to actin organization, generating functional redundancy in the pathways that regulate actin cytoskeletal remodeling. [provided by RefSeq, Dec 2008]

EPS8L2 Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive 106
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

EPS8L2 links:

Genome browser will be placed here

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=0.16192743).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021008.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DEAF1	NM_021008.4	MANE Select	c.80C>A	p.Ala27Glu	missense	Exon 1 of 12	NP_066288.2
DEAF1	NM_001440883.1		c.80C>A	p.Ala27Glu	missense	Exon 1 of 11	NP_001427812.1
DEAF1	NM_001440884.1		c.80C>A	p.Ala27Glu	missense	Exon 1 of 11	NP_001427813.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DEAF1	ENST00000382409.4	TSL:1 MANE Select	c.80C>A	p.Ala27Glu	missense	Exon 1 of 12	ENSP00000371846.3
DEAF1	ENST00000687329.1		n.-125C>A		non_coding_transcript_exon	Exon 1 of 13	ENSP00000510598.1
DEAF1	ENST00000692634.1		n.-125C>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000508859.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

920106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

440602

African (AFR)

AF:

0.00

AC:

AN:

17294

American (AMR)

AF:

0.00

AC:

AN:

4312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9698

East Asian (EAS)

AF:

0.00

AC:

AN:

12152

South Asian (SAS)

AF:

0.00

AC:

AN:

25072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7726

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2146

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

809274

Other (OTH)

AF:

0.00

AC:

AN:

32432

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.53

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

0.76

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.30

REVEL

Benign

0.056

Sift

Benign

0.18

Sift4G

Uncertain

0.0090

Polyphen

0.023

Vest4

0.20

MutPred

0.34

Gain of relative solvent accessibility (P = 0.09)

MVP

0.57

MPC

1.7

ClinPred

0.34

GERP RS

2.4

PromoterAI

-0.040

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.22

gMVP

0.55

Mutation Taster

=72/28

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.

chr11-694968-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over