rs758787132

Variant names:

• chr11-694829-G-T
• rs758787132
• NM_021008.4:c.219C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-694829-G-T
• chr11-694829-G-A
• chr11-694829-G-C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2 BP4_Moderate BP6_Very_Strong BP7

The NM_021008.4(DEAF1):​c.219C>A​(p.Pro73Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000023 in 1,306,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: DEAF1 NM_021008.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.47
• 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: Benign. The variant received -9 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 11-694829-G-T is Benign according to our data. Variant chr11-694829-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 434928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.47 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.219C>A	p.Pro73Pro	synonymous	Exon 1 of 12	NP_066288.2
	DEAF1	NM_001440883.1		c.219C>A	p.Pro73Pro	synonymous	Exon 1 of 11	NP_001427812.1
	DEAF1	NM_001440884.1		c.219C>A	p.Pro73Pro	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.219C>A	p.Pro73Pro	synonymous	Exon 1 of 12	ENSP00000371846.3	O75398-1
	DEAF1	ENST00000882097.1		c.219C>A	p.Pro73Pro	synonymous	Exon 1 of 13	ENSP00000552156.1
	DEAF1	ENST00000685854.1		c.15C>A	p.Pro5Pro	synonymous	Exon 1 of 14	ENSP00000508801.1	A0A8I5KQY1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000185 AC: 2 AN: 107980 AF XY: 0.0000160

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: 0.0000424

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000230 AC: 3 AN: 1306598 Hom.: 0 Cov.: 32 AF XY: 0.00000155 AC XY: 1 AN XY: 646540

African (AFR) AF: 0.00 AC: 0 AN: 27096

American (AMR) AF: 0.00 AC: 0 AN: 28272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22292

East Asian (EAS) AF: 0.00 AC: 0 AN: 28598

South Asian (SAS) AF: 0.00 AC: 0 AN: 68588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3878

European-Non Finnish (NFE) AF: 0.00000288 AC: 3 AN: 1041114

Other (OTH) AF: 0.00 AC: 0 AN: 53478

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	8.9
DANN	Benign	0.94
PhyloP100		1.5
PromoterAI		0.034	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

dbSNP: rs758787132; hg19: chr11-694829;