9-123391655-G-A

Position:

• chr9-123391655-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND1A	NM_001352964.2	c.1632-3797C>T		intron_variant		ENST00000394215.7	NP_001339893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND1A	ENST00000394215.7	c.1632-3797C>T		intron_variant		5	NM_001352964.2	ENSP00000377763.4
DENND1A	ENST00000473039.5	n.1441-3797C>T		intron_variant		1
DENND1A	ENST00000373624.6	c.1578-7742C>T		intron_variant		5		ENSP00000362727.2

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

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.533

Alfa AF: 0.604 Hom.: 12828

Bravo AF: 0.510

Asia WGS AF: 0.389 AC: 1356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2491352; hg19: chr9-126153934; COSMIC: COSV65357569;