NM_182765.6:c.418G>C

Variant names:

• chr10-91461264-G-C
• rs762055828
• NM_182765.6:c.418G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_182765.6(HECTD2):​c.418G>C​(p.Glu140Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,337,494 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: 0.000011 (0 hom.)
• Consequence: HECTD2 NM_182765.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.31
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29637134).
• BS2: High AC in GnomAdExome4 at 15 AD gene.

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.418G>C	p.Glu140Gln	missense	Exon 4 of 21	NP_877497.4	Q5U5R9-1
	HECTD2	NM_001284274.3		c.418G>C	p.Glu140Gln	missense	Exon 4 of 22	NP_001271203.2	E7ERR3
	HECTD2	NM_001348365.2		c.97G>C	p.Glu33Gln	missense	Exon 4 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.418G>C	p.Glu140Gln	missense	Exon 4 of 21	ENSP00000298068.5	Q5U5R9-1
	HECTD2	ENST00000446394.5	TSL:2	c.418G>C	p.Glu140Gln	missense	Exon 4 of 22	ENSP00000401023.1	E7ERR3
	HECTD2	ENST00000371681.8	TSL:2	c.418G>C	p.Glu140Gln	missense	Exon 4 of 5	ENSP00000360746.4	Q5U5R9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000148 AC: 3 AN: 203364 AF XY: 0.0000179

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000301

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000112 AC: 15 AN: 1337494 Hom.: 0 Cov.: 20 AF XY: 0.0000194 AC XY: 13 AN XY: 669566

African (AFR) AF: 0.00 AC: 0 AN: 26592

American (AMR) AF: 0.00 AC: 0 AN: 31574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24352

East Asian (EAS) AF: 0.00 AC: 0 AN: 35376

South Asian (SAS) AF: 0.00 AC: 0 AN: 75042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5498

European-Non Finnish (NFE) AF: 0.0000136 AC: 14 AN: 1030614

Other (OTH) AF: 0.0000179 AC: 1 AN: 55716

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000901 Hom.: 0

Bravo AF: 0.0000113

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

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	0.092
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.97	L
PhyloP100		8.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.14
Sift	Benign	0.064	T
Sift4G	Benign	0.12	T
Polyphen		0.68	P
Vest4		0.41
MutPred		0.29		Gain of helix (P = 0.0425)
MVP		0.30
MPC		0.52
ClinPred		0.50	D
GERP RS		5.1
Varity_R		0.23
gMVP		0.51
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs762055828; hg19: chr10-93221021;