chr11-8707189-C-T

Variant names:

• chr11-8707189-C-T
• rs149402828
• NM_213618.2:c.2467G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_213618.2(DENND2B):​c.2467G>A​(p.Ala823Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,613,506 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (37 hom.)
• Consequence: DENND2B NM_213618.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.21
• Publications: 7 publications found

Genes affected

DENND2B (HGNC:11350): (DENN domain containing 2B) This gene was identified by its ability to suppress the tumorigenicity of Hela cells in nude mice. The protein encoded by this gene contains a C-terminal region that shares similarity with the Rab 3 family of small GTP binding proteins. This protein preferentially binds to the SH3 domain of c-Abl kinase, and acts as a regulator of MAPK1/ERK2 kinase, which may contribute to its ability to reduce the tumorigenic phenotype in cells. Three alternatively spliced transcript variants of this gene encoding distinct isoforms are identified. [provided by RefSeq, Jul 2008]

RPL27A (HGNC:10329): (ribosomal protein L27a) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L15P family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, multiple processed pseudogenes derived from this gene are dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009617209).
• BP6: Variant 11-8707189-C-T is Benign according to our data. Variant chr11-8707189-C-T is described in ClinVar as Benign. ClinVar VariationId is 769795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00174 (265/152340) while in subpopulation EAS AF = 0.0185 (96/5178). AF 95% confidence interval is 0.0155. There are 2 homozygotes in GnomAd4. There are 152 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213618.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2B	NM_213618.2	MANE Select	c.2467G>A	p.Ala823Thr	missense	Exon 13 of 20	NP_998783.1	P78524-1
	DENND2B	NM_001376495.1		c.2467G>A	p.Ala823Thr	missense	Exon 17 of 24	NP_001363424.1	P78524-1
	DENND2B	NM_001376496.1		c.2467G>A	p.Ala823Thr	missense	Exon 15 of 22	NP_001363425.1	P78524-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2B	ENST00000313726.11	TSL:1 MANE Select	c.2467G>A	p.Ala823Thr	missense	Exon 13 of 20	ENSP00000319678.6	P78524-1
	DENND2B	ENST00000534127.5	TSL:1	c.2467G>A	p.Ala823Thr	missense	Exon 16 of 23	ENSP00000433528.1	P78524-1
	DENND2B	ENST00000526757.5	TSL:1	c.1207G>A	p.Ala403Thr	missense	Exon 12 of 19	ENSP00000435097.1	P78524-2

Frequencies

GnomAD3 genomes AF: 0.00175 AC: 266 AN: 152222 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00303 AC: 760 AN: 251022 AF XY: 0.00246

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.0132

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0140

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00134 AC: 1956 AN: 1461166 Hom.: 37 Cov.: 31 AF XY: 0.00127 AC XY: 920 AN XY: 726832

African (AFR) AF: 0.000179 AC: 6 AN: 33476

American (AMR) AF: 0.0130 AC: 583 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.0294 AC: 1167 AN: 39682

South Asian (SAS) AF: 0.000964 AC: 83 AN: 86066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1111616

Other (OTH) AF: 0.00134 AC: 81 AN: 60370

GnomAD4 genome AF: 0.00174 AC: 265 AN: 152340 Hom.: 2 Cov.: 32 AF XY: 0.00204 AC XY: 152 AN XY: 74506

African (AFR) AF: 0.000649 AC: 27 AN: 41578

American (AMR) AF: 0.00823 AC: 126 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0185 AC: 96 AN: 5178

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00101 Hom.: 1

Bravo AF: 0.00219

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00268 AC: 325

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.0066
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.2
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.19
Sift	Benign	0.18	T
Sift4G	Benign	0.25	T
Polyphen		0.018	B
Vest4		0.59
MVP		0.51
MPC		1.3
ClinPred		0.042	T
GERP RS		5.1
Varity_R		0.18
gMVP		0.45
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs149402828; hg19: chr11-8728736; COSMIC: COSV100567176; COSMIC: COSV100567176;