10-91501045-A-G

Variant names:

• chr10-91501045-A-G
• rs1360187
• NM_182765.6:c.2067-146A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182765.6(HECTD2):​c.2067-146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 624,248 control chromosomes in the GnomAD database, including 10,097 homozygotes. 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 0.20 (7282 hom., cov: 32)
  • Exomes 𝑓: 0.066 (2815 hom.)
• Consequence: HECTD2 NM_182765.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD2	NM_182765.6	MANE Select	c.2067-146A>G		intron	N/A	NP_877497.4
	HECTD2	NM_001284274.3		c.2079-146A>G		intron	N/A	NP_001271203.2
	HECTD2	NM_001348365.2		c.1746-146A>G		intron	N/A	NP_001335294.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD2	ENST00000298068.10	TSL:1 MANE Select	c.2067-146A>G		intron	N/A	ENSP00000298068.5
	HECTD2	ENST00000371667.1	TSL:1	c.1017-146A>G		intron	N/A	ENSP00000360731.1
	HECTD2	ENST00000446394.5	TSL:2	c.2079-146A>G		intron	N/A	ENSP00000401023.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30481 AN: 151962 Hom.: 7261 Cov.: 32

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.0825

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.0341

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.0659 AC: 31109 AN: 472168 Hom.: 2815 AF XY: 0.0623 AC XY: 15918 AN XY: 255560

African (AFR) AF: 0.581 AC: 6690 AN: 11524

American (AMR) AF: 0.0670 AC: 992 AN: 14802

Ashkenazi Jewish (ASJ) AF: 0.0890 AC: 1325 AN: 14894

East Asian (EAS) AF: 0.0876 AC: 2504 AN: 28600

South Asian (SAS) AF: 0.0333 AC: 1451 AN: 43532

European-Finnish (FIN) AF: 0.0322 AC: 1186 AN: 36806

Middle Eastern (MID) AF: 0.0998 AC: 208 AN: 2084

European-Non Finnish (NFE) AF: 0.0488 AC: 14359 AN: 294166

Other (OTH) AF: 0.0929 AC: 2394 AN: 25760

GnomAD4 genome AF: 0.201 AC: 30543 AN: 152080 Hom.: 7282 Cov.: 32 AF XY: 0.195 AC XY: 14503 AN XY: 74372

African (AFR) AF: 0.579 AC: 23979 AN: 41442

American (AMR) AF: 0.0891 AC: 1362 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0974 AC: 338 AN: 3472

East Asian (EAS) AF: 0.0825 AC: 428 AN: 5190

South Asian (SAS) AF: 0.0352 AC: 170 AN: 4830

European-Finnish (FIN) AF: 0.0341 AC: 360 AN: 10570

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0500 AC: 3395 AN: 67966

Other (OTH) AF: 0.163 AC: 344 AN: 2114

Alfa AF: 0.133 Hom.: 519

Bravo AF: 0.222

Asia WGS AF: 0.108 AC: 373 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.80
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs1360187; hg19: chr10-93260802;