10-91461320-G-C

Variant names:

• chr10-91461320-G-C
• NM_182765.6:c.474G>C
• HECTD2 p.Thr158Thr

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_182765.6(HECTD2):​c.474G>C​(p.Thr158Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HECTD2 NM_182765.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.396 with no splicing effect.

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.474G>C	p.Thr158Thr	synonymous	Exon 4 of 21	NP_877497.4	Q5U5R9-1
	HECTD2	NM_001284274.3		c.474G>C	p.Thr158Thr	synonymous	Exon 4 of 22	NP_001271203.2	E7ERR3
	HECTD2	NM_001348365.2		c.153G>C	p.Thr51Thr	synonymous	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.474G>C	p.Thr158Thr	synonymous	Exon 4 of 21	ENSP00000298068.5	Q5U5R9-1
	HECTD2	ENST00000446394.5	TSL:2	c.474G>C	p.Thr158Thr	synonymous	Exon 4 of 22	ENSP00000401023.1	E7ERR3
	HECTD2	ENST00000371681.8	TSL:2	c.474G>C	p.Thr158Thr	synonymous	Exon 4 of 5	ENSP00000360746.4	Q5U5R9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.4
DANN	Benign	0.60
PhyloP100		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-93221077;