rs2479106

chr9-123762933-A-Gchr9-123762933-A-T

Variant summary

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

The NM_001352964.2(DENND1A):c.183-5111T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,984 control chromosomes in the GnomAD database, including 17,040 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 0.43 (17040 hom., cov: 32)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388

Genes affected

DENND1A (HGNC:29324): (DENN domain containing 1A) Clathrin (see MIM 118955)-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1A, function as guanine nucleotide exchange factors (GEFs) for the early endosomal small GTPase RAB35 (MIM 604199) and bind to clathrin and clathrin adaptor protein-2 (AP2; see MIM 601024). Thus, connecdenns link RAB35 activation with the clathrin machinery (Marat and McPherson, 2010 [PubMed 20154091]).[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DENND1A	NM_001352964.2	c.183-5111T>C		intron_variant		ENST00000394215.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DENND1A	ENST00000394215.7	c.183-5111T>C		intron_variant		5	NM_001352964.2	A2

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64669 AN: 151866 Hom.: 16979 Cov.: 32

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.426 AC: 64805 AN: 151984 Hom.: 17040 Cov.: 32 AF XY: 0.428 AC XY: 31787 AN XY: 74314

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.365

Alfa AF: 0.310 Hom.: 18010

Bravo AF: 0.431

Asia WGS AF: 0.296 AC: 1028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.0
Dann	Benign	0.75

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: rs2479106; hg19: chr9-126525212;