rs12249854

Variant names:

• chr10-91426505-T-A
• rs12249854
• NM_182765.6:c.268+1095T>A

Variant summary

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

The NM_182765.6(HECTD2):​c.268+1095T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 151,830 control chromosomes in the GnomAD database, including 7,225 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 (7225 hom., cov: 31)
• Consequence: HECTD2 NM_182765.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810
• Publications: 8 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD2	NM_182765.6	MANE Select	c.268+1095T>A		intron	N/A	NP_877497.4	Q5U5R9-1
	HECTD2	NM_001284274.3		c.268+1095T>A		intron	N/A	NP_001271203.2	E7ERR3
	HECTD2	NM_001348365.2		c.-54+1095T>A		intron	N/A	NP_001335294.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD2	ENST00000298068.10	TSL:1 MANE Select	c.268+1095T>A		intron	N/A	ENSP00000298068.5	Q5U5R9-1
	HECTD2	ENST00000446394.5	TSL:2	c.268+1095T>A		intron	N/A	ENSP00000401023.1	E7ERR3
	HECTD2	ENST00000371681.8	TSL:2	c.268+1095T>A		intron	N/A	ENSP00000360746.4	Q5U5R9-2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30330 AN: 151712 Hom.: 7204 Cov.: 31

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0889

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.0828

Gnomad SAS AF: 0.0351

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.162

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.200 AC: 30392 AN: 151830 Hom.: 7225 Cov.: 31 AF XY: 0.195 AC XY: 14445 AN XY: 74234

African (AFR) AF: 0.577 AC: 23856 AN: 41318

American (AMR) AF: 0.0888 AC: 1352 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 334 AN: 3462

East Asian (EAS) AF: 0.0828 AC: 427 AN: 5156

South Asian (SAS) AF: 0.0351 AC: 169 AN: 4814

European-Finnish (FIN) AF: 0.0339 AC: 360 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0499 AC: 3388 AN: 67920

Other (OTH) AF: 0.162 AC: 341 AN: 2106

Alfa AF: 0.132 Hom.: 520

Bravo AF: 0.222

Asia WGS AF: 0.108 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.061
DANN	Benign	0.52
PhyloP100		-0.81
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: rs12249854; hg19: chr10-93186262;