NM_021008.4:c.282C>T

Variant names:

• chr11-694766-G-A
• NM_021008.4:c.282C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_021008.4(DEAF1):​c.282C>T​(p.Ala94Ala) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEAF1 NM_021008.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.211
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 11-694766-G-A is Benign according to our data. Variant chr11-694766-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3727444.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.211 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEAF1	NM_021008.4	MANE Select	c.282C>T	p.Ala94Ala	synonymous	Exon 1 of 12	NP_066288.2
	DEAF1	NM_001440883.1		c.282C>T	p.Ala94Ala	synonymous	Exon 1 of 11	NP_001427812.1
	DEAF1	NM_001440884.1		c.282C>T	p.Ala94Ala	synonymous	Exon 1 of 11	NP_001427813.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEAF1	ENST00000382409.4	TSL:1 MANE Select	c.282C>T	p.Ala94Ala	synonymous	Exon 1 of 12	ENSP00000371846.3	O75398-1
	DEAF1	ENST00000882097.1		c.282C>T	p.Ala94Ala	synonymous	Exon 1 of 13	ENSP00000552156.1
	DEAF1	ENST00000685854.1		c.78C>T	p.Ala26Ala	synonymous	Exon 1 of 14	ENSP00000508801.1	A0A8I5KQY1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1155118 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 557768

African (AFR) AF: 0.00 AC: 0 AN: 23170

American (AMR) AF: 0.00 AC: 0 AN: 9078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15380

East Asian (EAS) AF: 0.00 AC: 0 AN: 26386

South Asian (SAS) AF: 0.00 AC: 0 AN: 39572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3196

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 965662

Other (OTH) AF: 0.00 AC: 0 AN: 46782

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Uncertain	0.98
PhyloP100		0.21
PromoterAI		0.0050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

hg19: chr11-694766;