rs2363830

Variant names:

• chr7-140531206-T-G
• rs2363830
• NM_015689.5:c.2328-3711A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015689.5. 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
	DENND2A	NM_015689.5	MANE Select	c.2328-3711A>C		intron	N/A	NP_056504.3
	DENND2A	NM_001318052.2		c.2328-3711A>C		intron	N/A	NP_001304981.1
	DENND2A	NM_001362678.2		c.2328-3711A>C		intron	N/A	NP_001349607.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2A	ENST00000496613.6	TSL:2 MANE Select	c.2328-3711A>C		intron	N/A	ENSP00000419654.1
	DENND2A	ENST00000275884.10	TSL:1	c.2328-3711A>C		intron	N/A	ENSP00000275884.6
	DENND2A	ENST00000537639.5	TSL:1	c.2328-3711A>C		intron	N/A	ENSP00000442245.1

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

African (AFR) AF: 0.285 AC: 11816 AN: 41518

American (AMR) AF: 0.0764 AC: 1168 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 363 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5190

South Asian (SAS) AF: 0.0945 AC: 456 AN: 4826

European-Finnish (FIN) AF: 0.0208 AC: 221 AN: 10622

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0739 AC: 5027 AN: 68008

Other (OTH) AF: 0.117 AC: 247 AN: 2110

Alfa AF: 0.0835 Hom.: 578

Bravo AF: 0.138

Asia WGS AF: 0.0570 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.61
PhyloP100		0.31
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: rs2363830; hg19: chr7-140231006;