1-111194050-T-C

Position:

• chr1-111194050-T-C

Variant summary

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

The NM_024901.5(DENND2D):​c.794+528A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,252 control chromosomes in the GnomAD database, including 2,253 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 0.17 (2253 hom., cov: 32)
• Consequence: DENND2D NM_024901.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND2D	NM_024901.5	c.794+528A>G		intron_variant		ENST00000357640.9	NP_079177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND2D	ENST00000357640.9	c.794+528A>G		intron_variant		1	NM_024901.5	ENSP00000350266	P4
DENND2D	ENST00000369752.5	c.785+528A>G		intron_variant		2		ENSP00000358767	A1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25560 AN: 152134 Hom.: 2246 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.168 AC: 25600 AN: 152252 Hom.: 2253 Cov.: 32 AF XY: 0.165 AC XY: 12289 AN XY: 74446

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.181

Alfa AF: 0.175 Hom.: 3241

Bravo AF: 0.164

Asia WGS AF: 0.0960 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.3
DANN	Benign	0.83

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: rs656843; hg19: chr1-111736672;