Genetic Variant NM_021008.4:c.264G>T (chr11-694784-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_021008.4(DEAF1):c.264G>T(p.Glu88Asp) 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 (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DEAF1
NM_021008.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.90

Publications

0 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: 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3584511).

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.264G>T	p.Glu88Asp	missense	Exon 1 of 12	NP_066288.2
DEAF1	NM_001440885.1		c.-333G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001427814.1
DEAF1	NM_001440886.1		c.-1733G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_001427815.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DEAF1	ENST00000382409.4	TSL:1 MANE Select	c.264G>T	p.Glu88Asp	missense	Exon 1 of 12	ENSP00000371846.3	O75398-1
DEAF1	ENST00000882097.1		c.264G>T	p.Glu88Asp	missense	Exon 1 of 13	ENSP00000552156.1
DEAF1	ENST00000685854.1		c.60G>T	p.Glu20Asp	missense	Exon 1 of 14	ENSP00000508801.1	A0A8I5KQY1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1189332

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

577282

African (AFR)

AF:

0.00

AC:

AN:

23522

American (AMR)

AF:

0.00

AC:

AN:

10324

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16662

East Asian (EAS)

AF:

0.00

AC:

AN:

26600

South Asian (SAS)

AF:

0.00

AC:

AN:

47958

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3364

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

984058

Other (OTH)

AF:

0.00

AC:

AN:

48594

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.75

M_CAP

Pathogenic

0.88

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.7

PhyloP100

1.9

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

0.11

REVEL

Benign

0.22

Sift

Benign

0.14

Sift4G

Benign

0.38

Polyphen

0.98

Vest4

0.041

MutPred

0.16

Loss of helix (P = 0.028)

MVP

0.73

MPC

0.66

ClinPred

0.72

GERP RS

2.6

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.067

gMVP

0.25

Mutation Taster

=84/16

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over