rs7081363

Positions:

• chr10-91410192-G-A
• chr10-91410192-G-C
• chr10-91410192-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_024467.1(HECTD2-AS1):​n.427-59313C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 151,772 control chromosomes in the GnomAD database, including 6,289 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 0.19 (6289 hom., cov: 32)
  • Exomes 𝑓: 0.043 (0 hom.)
• Consequence: HECTD2-AS1 NR_024467.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HECTD2-AS1	NR_024467.1	n.427-59313C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000688440.1	n.322-59313C>T		intron_variant, non_coding_transcript_variant
HECTD2	ENST00000631422.1	c.-184+771G>A		intron_variant		3
	ENST00000700888.1	n.219-59313C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28427 AN: 151426 Hom.: 6269 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.0821

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0475

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.0431 AC: 10 AN: 232 Hom.: 0 AF XY: 0.0317 AC XY: 4 AN XY: 126

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.0256

Gnomad4 NFE exome AF: 0.0493

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.188 AC: 28488 AN: 151540 Hom.: 6289 Cov.: 32 AF XY: 0.183 AC XY: 13556 AN XY: 74094

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.0846

Gnomad4 ASJ AF: 0.0971

Gnomad4 EAS AF: 0.0821

Gnomad4 SAS AF: 0.0352

Gnomad4 FIN AF: 0.0340

Gnomad4 NFE AF: 0.0475

Gnomad4 OTH AF: 0.149

Alfa AF: 0.0211 Hom.: 25

Bravo AF: 0.207

Asia WGS AF: 0.105 AC: 365 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.9
DANN	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7081363; hg19: chr10-93169949;