rs2491352

Variant names:

• chr9-123391655-G-A
• rs2491352
• NM_001352964.2:c.1632-3797C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-123391655-G-A
• chr9-123391655-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001352964.2(DENND1A):​c.1632-3797C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 150,796 control chromosomes in the GnomAD database, including 22,471 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 0.53 (22471 hom., cov: 29)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352964.2. 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
	DENND1A	NM_001352964.2	MANE Select	c.1632-3797C>T		intron	N/A	NP_001339893.1	A0A0A0MS48
	DENND1A	NM_001393654.1		c.1578-3797C>T		intron	N/A	NP_001380583.1
	DENND1A	NM_001352965.2		c.1482-3797C>T		intron	N/A	NP_001339894.1	Q8TEH3-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND1A	ENST00000394215.7	TSL:5 MANE Select	c.1632-3797C>T		intron	N/A	ENSP00000377763.4	A0A0A0MS48
	DENND1A	ENST00000473039.5	TSL:1	n.1441-3797C>T		intron	N/A
	DENND1A	ENST00000866226.1		c.1578-3797C>T		intron	N/A	ENSP00000536285.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80368 AN: 150684 Hom.: 22479 Cov.: 29

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.590

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.533 AC: 80355 AN: 150796 Hom.: 22471 Cov.: 29 AF XY: 0.526 AC XY: 38723 AN XY: 73568

African (AFR) AF: 0.369 AC: 15132 AN: 40980

American (AMR) AF: 0.477 AC: 7196 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2073 AN: 3456

East Asian (EAS) AF: 0.394 AC: 1995 AN: 5064

South Asian (SAS) AF: 0.459 AC: 2189 AN: 4774

European-Finnish (FIN) AF: 0.583 AC: 6020 AN: 10318

Middle Eastern (MID) AF: 0.590 AC: 170 AN: 288

European-Non Finnish (NFE) AF: 0.648 AC: 43926 AN: 67836

Other (OTH) AF: 0.533 AC: 1119 AN: 2098

Alfa AF: 0.605 Hom.: 14486

Bravo AF: 0.510

Asia WGS AF: 0.389 AC: 1356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Benign	0.78
PhyloP100		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2491352; hg19: chr9-126153934; COSMIC: COSV65357569;