10-91425322-C-T

Variant names:

• chr10-91425322-C-T
• rs751812903
• NM_182765.6:c.180C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_182765.6(HECTD2):​c.180C>T​(p.Ser60Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,038 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HECTD2 NM_182765.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=2.93 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.180C>T	p.Ser60Ser	synonymous	Exon 2 of 21	NP_877497.4	Q5U5R9-1
	HECTD2	NM_001284274.3		c.180C>T	p.Ser60Ser	synonymous	Exon 2 of 22	NP_001271203.2	E7ERR3
	HECTD2	NM_173497.4		c.180C>T	p.Ser60Ser	synonymous	Exon 2 of 5	NP_775768.4	Q5U5R9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD2	ENST00000298068.10	TSL:1 MANE Select	c.180C>T	p.Ser60Ser	synonymous	Exon 2 of 21	ENSP00000298068.5	Q5U5R9-1
	HECTD2	ENST00000446394.5	TSL:2	c.180C>T	p.Ser60Ser	synonymous	Exon 2 of 22	ENSP00000401023.1	E7ERR3
	HECTD2	ENST00000371681.8	TSL:2	c.180C>T	p.Ser60Ser	synonymous	Exon 2 of 5	ENSP00000360746.4	Q5U5R9-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152038 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1388968 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 690386

African (AFR) AF: 0.00 AC: 0 AN: 31528

American (AMR) AF: 0.00 AC: 0 AN: 40228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24540

East Asian (EAS) AF: 0.00 AC: 0 AN: 37424

South Asian (SAS) AF: 0.00 AC: 0 AN: 73664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5490

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069262

Other (OTH) AF: 0.00 AC: 0 AN: 56374

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152038 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74260

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		2.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs751812903; hg19: chr10-93185079;