1-111193767-C-T

Position:

• chr1-111193767-C-T

Variant summary

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

The NM_024901.5(DENND2D):​c.794+811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,086 control chromosomes in the GnomAD database, including 41,428 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 0.73 (41428 hom., cov: 31)
• Consequence: DENND2D NM_024901.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

Genes affected

DENND2D (HGNC:26192): (DENN domain containing 2D) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Located in cytosol and nucleoplasm. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DENND2D	NM_024901.5	c.794+811G>A		intron_variant		ENST00000357640.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DENND2D	ENST00000357640.9	c.794+811G>A		intron_variant		1	NM_024901.5	P4
DENND2D	ENST00000369752.5	c.785+811G>A		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111574 AN: 151968 Hom.: 41355 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.735 AC: 111710 AN: 152086 Hom.: 41428 Cov.: 31 AF XY: 0.736 AC XY: 54748 AN XY: 74338

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.699

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.722

Alfa AF: 0.686 Hom.: 47270

Bravo AF: 0.742

Asia WGS AF: 0.779 AC: 2710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.54
DANN	Benign	0.59

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: rs657801; hg19: chr1-111736389;