Variant chr10-91410526-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182765.6(HECTD2):c.88G>C(p.Glu30Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000755 in 1,324,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

HECTD2
NM_182765.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

Variant links:

Genes affected

HECTD2 (HGNC:26736): (HECT domain E3 ubiquitin protein ligase 2) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in protein ubiquitination. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

HECTD2 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09713298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HECTD2	NM_182765.6 linkuse as main transcript	c.88G>C	p.Glu30Gln	missense_variant	1/21	ENST00000298068.10	NP_877497.4
HECTD2-AS1	NR_024467.1 linkuse as main transcript	n.427-59647C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HECTD2	ENST00000298068.10 linkuse as main transcript	c.88G>C	p.Glu30Gln	missense_variant	1/21	1	NM_182765.6	ENSP00000298068	P4	Q5U5R9-1
	ENST00000688440.1 linkuse as main transcript	n.322-59647C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.55e-7

AC:

AN:

1324898

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

654228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.53e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 21, 2024

The c.88G>C (p.E30Q) alteration is located in exon 1 (coding exon 1) of the HECTD2 gene. This alteration results from a G to C substitution at nucleotide position 88, causing the glutamic acid (E) at amino acid position 30 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0094

T;.;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.70

T;T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.097

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

.;N;N

MutationTaster

Benign

0.75

N;N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.37

N;N;N

REVEL

Benign

0.021

Sift

Benign

0.33

T;T;T

Sift4G

Benign

0.48

T;T;T

Polyphen

0.028

B;.;B

Vest4

0.12

MutPred

0.089

Gain of methylation at K33 (P = 0.1108);Gain of methylation at K33 (P = 0.1108);Gain of methylation at K33 (P = 0.1108);

MVP

0.15

MPC

0.47

ClinPred

0.19

GERP RS

2.0

Varity_R

0.16

gMVP

0.25

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over