rs2363830

Positions:

• chr7-140531206-T-G

Variant summary

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

The NM_015689.5(DENND2A):​c.2328-3711A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,238 control chromosomes in the GnomAD database, including 2,001 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 0.13 (2001 hom., cov: 32)
• Consequence: DENND2A NM_015689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

Genes affected

DENND2A (HGNC:22212): (DENN domain containing 2A) Enables guanyl-nucleotide exchange factor activity. Involved in retrograde transport, endosome to Golgi. Located in actin cytoskeleton. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DENND2A	NM_015689.5	c.2328-3711A>C		intron_variant		ENST00000496613.6
DENND2A	NM_001318052.2	c.2328-3711A>C		intron_variant
DENND2A	NM_001362678.2	c.2328-3711A>C		intron_variant
DENND2A	NR_134477.1	n.2473-3769A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DENND2A	ENST00000496613.6	c.2328-3711A>C		intron_variant		2	NM_015689.5	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19342 AN: 152120 Hom.: 1993 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.0765

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0942

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0739

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.127 AC: 19383 AN: 152238 Hom.: 2001 Cov.: 32 AF XY: 0.122 AC XY: 9082 AN XY: 74444

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.0764

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0945

Gnomad4 FIN AF: 0.0208

Gnomad4 NFE AF: 0.0739

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0859 Hom.: 458

Bravo AF: 0.138

Asia WGS AF: 0.0570 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.61

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: rs2363830; hg19: chr7-140231006;