Genetic Variant NM_015689.5:c.2328-3835G>T (chr7-140531330-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015689.5(DENND2A):c.2328-3835G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 152,164 control chromosomes in the GnomAD database, including 717 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 0.088 ( 717 hom., cov: 32)

Consequence

DENND2A
NM_015689.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.298

Publications

12 publications found

Variant links:

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]

DENND2A links:

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new If you want to explore the variant's impact on the transcript NM_015689.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DENND2A	NM_015689.5	MANE Select	c.2328-3835G>T	intron	N/A	NP_056504.3	Q9ULE3-1
DENND2A	NM_001318052.2		c.2328-3835G>T	intron	N/A	NP_001304981.1	Q9ULE3-1
DENND2A	NM_001362678.2		c.2328-3835G>T	intron	N/A	NP_001349607.1	Q9ULE3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DENND2A	ENST00000496613.6	TSL:2 MANE Select	c.2328-3835G>T	intron	N/A	ENSP00000419654.1	Q9ULE3-1
DENND2A	ENST00000275884.10	TSL:1	c.2328-3835G>T	intron	N/A	ENSP00000275884.6	Q9ULE3-1
DENND2A	ENST00000537639.5	TSL:1	c.2328-3835G>T	intron	N/A	ENSP00000442245.1	Q9ULE3-1

Frequencies

GnomAD3 genomes

AF:

0.0883

AC:

13426

AN:

152046

Hom.:

716

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.0615

Gnomad AMR

AF:

0.0623

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0719

Gnomad FIN

AF:

0.0201

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0732

Gnomad OTH

AF:

0.0826

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

GnomAD4 genome

AF:

0.0884

AC:

13452

AN:

152164

Hom.:

717

Cov.:

AF XY:

0.0853

AC XY:

6348

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.153

AC:

6346

AN:

41500

American (AMR)

AF:

0.0622

AC:

950

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

363

AN:

3472

East Asian (EAS)

AF:

0.000964

AC:

AN:

5188

South Asian (SAS)

AF:

0.0726

AC:

350

AN:

4820

European-Finnish (FIN)

AF:

0.0201

AC:

213

AN:

10594

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0732

AC:

4976

AN:

68016

Other (OTH)

AF:

0.0817

AC:

172

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

627

1253

1880

2506

3133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0773

Hom.:

1694

Bravo

AF:

0.0934

Asia WGS

AF:

0.0360

AC:

123

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.1

(source)

DANN

Benign

0.64

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over