Menu
GeneBe

10-91500606-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_182765.6(HECTD2):c.2055C>T(p.Asp685=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,558,110 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 48 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 45 hom. )

Consequence

HECTD2
NM_182765.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.33
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-91500606-C-T is Benign according to our data. Variant chr10-91500606-C-T is described in ClinVar as [Benign]. Clinvar id is 768377.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.33 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2171/152232) while in subpopulation AFR AF= 0.0494 (2051/41540). AF 95% confidence interval is 0.0476. There are 48 homozygotes in gnomad4. There are 1033 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 2166 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HECTD2NM_182765.6 linkuse as main transcriptc.2055C>T p.Asp685= synonymous_variant 19/21 ENST00000298068.10
HECTD2-AS1NR_024467.1 linkuse as main transcriptn.426+24422G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HECTD2ENST00000298068.10 linkuse as main transcriptc.2055C>T p.Asp685= synonymous_variant 19/211 NM_182765.6 P4Q5U5R9-1
ENST00000688440.1 linkuse as main transcriptn.321+24422G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0142
AC:
2166
AN:
152114
Hom.:
48
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0494
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00452
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00637
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.0138
GnomAD3 exomes
AF:
0.00382
AC:
958
AN:
250846
Hom.:
10
AF XY:
0.00282
AC XY:
382
AN XY:
135584
show subpopulations
Gnomad AFR exome
AF:
0.0516
Gnomad AMR exome
AF:
0.00171
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000361
Gnomad OTH exome
AF:
0.00245
GnomAD4 exome
AF:
0.00160
AC:
2251
AN:
1405878
Hom.:
45
Cov.:
24
AF XY:
0.00142
AC XY:
996
AN XY:
702788
show subpopulations
Gnomad4 AFR exome
AF:
0.0520
Gnomad4 AMR exome
AF:
0.00231
Gnomad4 ASJ exome
AF:
0.0000387
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000153
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000197
Gnomad4 OTH exome
AF:
0.00371
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0143
AC:
2171
AN:
152232
Hom.:
48
Cov.:
32
AF XY:
0.0139
AC XY:
1033
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.0494
Gnomad4 AMR
AF:
0.00451
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.0137
Alfa
AF:
0.00684
Hom.:
15
Bravo
AF:
0.0164
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.000491
EpiControl
AF:
0.000356

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
5.5
Dann
Benign
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs34553731; hg19: chr10-93260363; API