Genetic Variant NM_001080458.2:c.428-60G>A (chr2-176082509-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001080458.2(EVX2):c.428-60G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,481,788 control chromosomes in the GnomAD database, including 97,385 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.41 ( 13501 hom., cov: 34)

Exomes 𝑓: 0.35 ( 83884 hom. )

Consequence

EVX2
NM_001080458.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.149

Publications

3 publications found

Variant links:

Genes affected

EVX2 (HGNC:3507): (even-skipped homeobox 2) This gene is located at the 5' end of the HOXD gene cluster on chromosome 2. The encoded protein is a homeobox transcription factor that is related to the protein encoded by the Drosophila even-skipped (eve) gene, a member of the pair-rule class of segmentation genes. A 117 kb microdeletion at the 5' end of the HOXD gene cluster, which includes this gene and the HOXD9-HOXD13 genes, causes synpolydactyly, a dominantly inherited disease resulting in limb malformation. [provided by RefSeq, Sep 2009]

EVX2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVX2	NM_001080458.2 link	c.428-60G>A		intron_variant	Intron 1 of 2	ENST00000308618.5	NP_001073927.1	Q03828

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVX2	ENST00000308618.5 link	c.428-60G>A		intron_variant	Intron 1 of 2	5	NM_001080458.2	ENSP00000312385.4		Q03828

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61680

AN:

152068

Hom.:

13473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.543

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.492

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.440

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.383

GnomAD4 exome

AF:

0.350

AC:

465436

AN:

1329602

Hom.:

83884

AF XY:

0.352

AC XY:

228332

AN XY:

649576

show subpopulations

African (AFR)

AF:

0.540

AC:

14802

AN:

27412

American (AMR)

AF:

0.558

AC:

15000

AN:

26876

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

6590

AN:

18948

East Asian (EAS)

AF:

0.435

AC:

15611

AN:

35922

South Asian (SAS)

AF:

0.442

AC:

29852

AN:

67484

European-Finnish (FIN)

AF:

0.231

AC:

9953

AN:

43094

Middle Eastern (MID)

AF:

0.344

AC:

1312

AN:

3818

European-Non Finnish (NFE)

AF:

0.335

AC:

352191

AN:

1051298

Other (OTH)

AF:

0.368

AC:

20125

AN:

54750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

15453

30907

46360

61814

77267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12080

24160

36240

48320

60400

<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:

0.406

AC:

61774

AN:

152186

Hom.:

13501

Cov.:

AF XY:

0.405

AC XY:

30125

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.543

AC:

22547

AN:

41534

American (AMR)

AF:

0.492

AC:

7521

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1169

AN:

3472

East Asian (EAS)

AF:

0.421

AC:

2170

AN:

5160

South Asian (SAS)

AF:

0.442

AC:

2132

AN:

4828

European-Finnish (FIN)

AF:

0.235

AC:

2487

AN:

10604

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.332

AC:

22604

AN:

67992

Other (OTH)

AF:

0.384

AC:

813

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1737

3475

5212

6950

8687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.249

Hom.:

569

Bravo

AF:

0.428

Asia WGS

AF:

0.457

AC:

1589

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.7

(source)

DANN

Benign

0.95

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over