rs2133292304

Variant names:

• chr10-91485272-C-G
• rs2133292304
• NM_182765.6:c.1063C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-91485272-C-G
• chr10-91485272-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182765.6(HECTD2):​c.1063C>G​(p.His355Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,442,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HECTD2 NM_182765.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.38
• Publications: 0 publications found

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-AS1 (HGNC:):

HECTD2-AS1 (HGNC:48679): (HECTD2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38323566).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182765.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD2	NM_182765.6	MANE Select	c.1063C>G	p.His355Asp	missense	Exon 10 of 21	NP_877497.4	Q5U5R9-1
	HECTD2	NM_001284274.3		c.1075C>G	p.His359Asp	missense	Exon 11 of 22	NP_001271203.2	E7ERR3
	HECTD2	NM_001348365.2		c.742C>G	p.His248Asp	missense	Exon 10 of 21	NP_001335294.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD2	ENST00000298068.10	TSL:1 MANE Select	c.1063C>G	p.His355Asp	missense	Exon 10 of 21	ENSP00000298068.5	Q5U5R9-1
	HECTD2	ENST00000371667.1	TSL:1	c.13C>G	p.His5Asp	missense	Exon 2 of 13	ENSP00000360731.1	X6R824
	HECTD2	ENST00000498446.1	TSL:1	n.659C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442624 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 717494

African (AFR) AF: 0.00 AC: 0 AN: 32224

American (AMR) AF: 0.00 AC: 0 AN: 40898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25748

East Asian (EAS) AF: 0.00 AC: 0 AN: 38618

South Asian (SAS) AF: 0.00 AC: 0 AN: 82366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1104482

Other (OTH) AF: 0.00 AC: 0 AN: 59630

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.030	T
Eigen	Benign	0.049
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.27
Sift	Benign	0.34	T
Sift4G	Benign	0.074	T
Polyphen		0.0010	B
Vest4		0.59
MutPred		0.45		Gain of helix (P = 0.0325)
MVP		0.32
MPC		1.6
ClinPred		0.80	D
GERP RS		5.6
Varity_R		0.29
gMVP		0.92
Mutation Taster		=247/53	polymorphism

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

Other links and lift over

dbSNP: rs2133292304; hg19: chr10-93245029;