chr11-694968-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021008.4(DEAF1):c.80C>T(p.Ala27Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,065,266 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts 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. A27G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 1 hom. )

Consequence

DEAF1
NM_021008.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2557372).

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>T	p.Ala27Val	missense	Exon 1 of 12	NP_066288.2
DEAF1	NM_001440883.1		c.80C>T	p.Ala27Val	missense	Exon 1 of 11	NP_001427812.1
DEAF1	NM_001440884.1		c.80C>T	p.Ala27Val	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>T	p.Ala27Val	missense	Exon 1 of 12	ENSP00000371846.3
DEAF1	ENST00000687329.1		n.-125C>T		non_coding_transcript_exon	Exon 1 of 13	ENSP00000510598.1
DEAF1	ENST00000692634.1		n.-125C>T		non_coding_transcript_exon	Exon 1 of 10	ENSP00000508859.1

Frequencies

GnomAD3 genomes

AF:

0.00000689

AC:

AN:

145150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000350

AC:

AN:

28542

AF XY:

0.0000534

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000759

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000163

AC:

AN:

920116

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

440610

show subpopulations

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:

25078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7726

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2146

European-Non Finnish (NFE)

AF:

0.0000161

AC:

AN:

809278

Other (OTH)

AF:

0.0000617

AC:

AN:

32432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.556

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

AF:

0.00000689

AC:

AN:

145150

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70722

show subpopulations

African (AFR)

AF:

0.0000249

AC:

AN:

40096

American (AMR)

AF:

0.00

AC:

AN:

14570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3330

East Asian (EAS)

AF:

0.00

AC:

AN:

4480

South Asian (SAS)

AF:

0.00

AC:

AN:

4086

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65910

Other (OTH)

AF:

0.00

AC:

AN:

2014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Intellectual disability, autosomal dominant 24;C4310683:Intellectual disability-epilepsy-extrapyramidal syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.60

M_CAP

Pathogenic

0.61

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.0

PhyloP100

0.76

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.34

REVEL

Benign

0.10

Sift

Benign

0.086

Sift4G

Uncertain

0.026

Polyphen

0.89

Vest4

0.18

MutPred

0.38

Gain of catalytic residue at A27 (P = 0.0143)

MVP

0.69

MPC

1.5

ClinPred

0.23

GERP RS

2.4

PromoterAI

-0.022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.083

gMVP

0.35

Mutation Taster

=74/26

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over