chr10-91501045-A-G

Position:

• chr10-91501045-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HECTD2	NM_182765.6	c.2067-146A>G		intron_variant		ENST00000298068.10	NP_877497.4
HECTD2-AS1	NR_024467.1	n.426+23983T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HECTD2	ENST00000298068.10	c.2067-146A>G		intron_variant		1	NM_182765.6	ENSP00000298068	P4
	ENST00000688440.1	n.321+23983T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome AF: 0.581

Gnomad4 AMR exome AF: 0.0670

Gnomad4 ASJ exome AF: 0.0890

Gnomad4 EAS exome AF: 0.0876

Gnomad4 SAS exome AF: 0.0333

Gnomad4 FIN exome AF: 0.0322

Gnomad4 NFE exome AF: 0.0488

Gnomad4 OTH exome AF: 0.0929

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

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.0891

Gnomad4 ASJ AF: 0.0974

Gnomad4 EAS AF: 0.0825

Gnomad4 SAS AF: 0.0352

Gnomad4 FIN AF: 0.0341

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.163

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs1360187; hg19: chr10-93260802;