Genetic Variant ENAH:p.Glu205_Leu222del (chr1-225519331-ATCCAGGCGTTCCTGCCGCTCCAGGCGTTCCTGCCGCTCCAGGCGTTCCTGCCGC-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_018212.6(ENAH):c.615_668delGCGGCAGGAACGCCTGGAGCGGCAGGAACGCCTGGAGCGGCAGGAACGCCTGGA(p.Glu205_Leu222del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000067 in 149,150 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Consequence

ENAH
NM_018212.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.04

Publications

5 publications found

Variant links:

Genes affected

ENAH (HGNC:18271): (ENAH actin regulator) This gene encodes a member of the enabled/ vasodilator-stimulated phosphoprotein. Members of this gene family are involved in actin-based motility. This protein is involved in regulating the assembly of actin filaments and modulates cell adhesion and motility. Alternate splice variants of this gene have been correlated with tumor invasiveness in certain tissues and these variants may serve as prognostic markers. A pseudogene of this gene is found on chromosome 3. [provided by RefSeq, Sep 2016]

ENAH links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_018212.6.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018212.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ENAH	NM_018212.6	MANE Select	c.615_668delGCGGCAGGAACGCCTGGAGCGGCAGGAACGCCTGGAGCGGCAGGAACGCCTGGA	p.Glu205_Leu222del	disruptive_inframe_deletion	Exon 5 of 14	NP_060682.2
ENAH	NM_001420159.1		c.672_725delGCGGCAGGAACGCCTGGAGCGGCAGGAACGCCTGGAGCGGCAGGAACGCCTGGA	p.Glu224_Leu241del	disruptive_inframe_deletion	Exon 6 of 16	NP_001407088.1
ENAH	NM_001420160.1		c.615_668delGCGGCAGGAACGCCTGGAGCGGCAGGAACGCCTGGAGCGGCAGGAACGCCTGGA	p.Glu205_Leu222del	disruptive_inframe_deletion	Exon 5 of 15	NP_001407089.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENAH	ENST00000366843.7	TSL:1 MANE Select	c.615_668delGCGGCAGGAACGCCTGGAGCGGCAGGAACGCCTGGAGCGGCAGGAACGCCTGGA	p.Glu205_Leu222del	disruptive_inframe_deletion	Exon 5 of 14	ENSP00000355808.2	Q8N8S7-2
ENAH	ENST00000366844.7	TSL:1	c.615_668delGCGGCAGGAACGCCTGGAGCGGCAGGAACGCCTGGAGCGGCAGGAACGCCTGGA	p.Glu205_Leu222del	disruptive_inframe_deletion	Exon 5 of 15	ENSP00000355809.2	Q8N8S7-1
ENAH	ENST00000497899.6	TSL:1	c.465_518delGCGGCAGGAACGCCTGGAGCGGCAGGAACGCCTGGAGCGGCAGGAACGCCTGGA	p.Glu155_Leu172del	disruptive_inframe_deletion	Exon 4 of 4	ENSP00000489106.1	A0A0U1RQP7

Frequencies

GnomAD3 genomes

AF:

0.00000670

AC:

AN:

149150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000149

Gnomad OTH

AF:

0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.00000670

AC:

AN:

149150

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72666

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40424

American (AMR)

AF:

0.00

AC:

AN:

15034

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3402

East Asian (EAS)

AF:

0.00

AC:

AN:

4958

South Asian (SAS)

AF:

0.00

AC:

AN:

4576

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10254

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67252

Other (OTH)

AF:

0.00

AC:

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000435

Hom.:

111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.0

Mutation Taster

=124/76

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over