chr1-111193767-C-T

Variant names:

• chr1-111193767-C-T
• rs657801
• NM_024901.5:c.794+811G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024901.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2D	NM_024901.5	MANE Select	c.794+811G>A		intron	N/A	NP_079177.2
	DENND2D	NM_001271833.2		c.785+811G>A		intron	N/A	NP_001258762.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2D	ENST00000357640.9	TSL:1 MANE Select	c.794+811G>A		intron	N/A	ENSP00000350266.4
	DENND2D	ENST00000369752.5	TSL:2	c.785+811G>A		intron	N/A	ENSP00000358767.5

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

African (AFR) AF: 0.830 AC: 34423 AN: 41486

American (AMR) AF: 0.795 AC: 12163 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1980 AN: 3466

East Asian (EAS) AF: 0.657 AC: 3391 AN: 5162

South Asian (SAS) AF: 0.804 AC: 3880 AN: 4826

European-Finnish (FIN) AF: 0.699 AC: 7387 AN: 10564

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46285 AN: 67980

Other (OTH) AF: 0.722 AC: 1521 AN: 2106

Alfa AF: 0.692 Hom.: 60800

Bravo AF: 0.742

Asia WGS AF: 0.779 AC: 2710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.54
DANN	Benign	0.59
PhyloP100		-0.023
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: rs657801; hg19: chr1-111736389;