Variant 2-196201240-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001348768.2(HECW2):c.*37G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 1,329,794 control chromosomes in the GnomAD database, including 338,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35244 hom., cov: 32)

Exomes 𝑓: 0.72 ( 303351 hom. )

Consequence

HECW2
NM_001348768.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0260

Variant links:

Genes affected

HECW2 (HGNC:29853): (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2) This gene encodes a member of a family of E3 ubiquitin ligases which plays an important role in the proliferation, migration and differentiation of neural crest cells as a regulator of glial cell line-derived neurotrophic factor (GDNF)/Ret signaling. This gene also plays an important role in angiogenesis through stabilization of endothelial cell-to-cell junctions as a regulator of angiomotin-like 1 stability. The encoded protein contains an N-terminal calcium/lipid-binding (C2) domain involved in membrane targeting, two-four WW domains responsible for cellular localization and substrate recognition, and a C-terminal homologous with E6-associated protein C-terminus (HECT) catalytic domain. Naturally occurring mutations in this gene are associated with neurodevelopmental delay, hypotonia, and epilepsy. The decreased expression of this gene in the aganglionic colon is associated with Hirschsprung's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

HECW2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-196201240-C-A is Benign according to our data. Variant chr2-196201240-C-A is described in ClinVar as [Benign]. Clinvar id is 1285331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HECW2	NM_001348768.2 linkuse as main transcript	c.*37G>T		3_prime_UTR_variant	29/29	ENST00000644978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HECW2	ENST00000644978.2 linkuse as main transcript	c.*37G>T		3_prime_UTR_variant	29/29		NM_001348768.2	P1	Q9P2P5-1

Frequencies

GnomAD3 genomes

AF:

0.677

AC:

102883

AN:

151936

Hom.:

35218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.567

Gnomad AMI

AF:

0.696

Gnomad AMR

AF:

0.715

Gnomad ASJ

AF:

0.684

Gnomad EAS

AF:

0.832

Gnomad SAS

AF:

0.748

Gnomad FIN

AF:

0.733

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.709

Gnomad OTH

AF:

0.685

GnomAD3 exomes

AF:

0.721

AC:

180561

AN:

250384

Hom.:

65478

AF XY:

0.723

AC XY:

97847

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.569

Gnomad AMR exome

AF:

0.753

Gnomad ASJ exome

AF:

0.688

Gnomad EAS exome

AF:

0.835

Gnomad SAS exome

AF:

0.754

Gnomad FIN exome

AF:

0.728

Gnomad NFE exome

AF:

0.708

Gnomad OTH exome

AF:

0.714

GnomAD4 exome

AF:

0.716

AC:

843778

AN:

1177740

Hom.:

303351

Cov.:

AF XY:

0.717

AC XY:

429906

AN XY:

599328

show subpopulations

Gnomad4 AFR exome

AF:

0.561

Gnomad4 AMR exome

AF:

0.752

Gnomad4 ASJ exome

AF:

0.687

Gnomad4 EAS exome

AF:

0.855

Gnomad4 SAS exome

AF:

0.753

Gnomad4 FIN exome

AF:

0.725

Gnomad4 NFE exome

AF:

0.711

Gnomad4 OTH exome

AF:

0.717

GnomAD4 genome

AF:

0.677

AC:

102951

AN:

152054

Hom.:

35244

Cov.:

AF XY:

0.679

AC XY:

50495

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.568

Gnomad4 AMR

AF:

0.715

Gnomad4 ASJ

AF:

0.684

Gnomad4 EAS

AF:

0.832

Gnomad4 SAS

AF:

0.748

Gnomad4 FIN

AF:

0.733

Gnomad4 NFE

AF:

0.709

Gnomad4 OTH

AF:

0.684

Alfa

AF:

0.698

Hom.:

37250

Bravo

AF:

0.672

Asia WGS

AF:

0.755

AC:

2627

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neurodevelopmental disorder with hypotonia, seizures, and absent language

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.90

DANN

Benign

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over