NM_001352964.2:c.303-3672G>A

Variant names:

• chr9-123680461-C-T
• rs10986087
• NM_001352964.2:c.303-3672G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352964.2(DENND1A):​c.303-3672G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,174 control chromosomes in the GnomAD database, including 9,197 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 0.34 (9197 hom., cov: 33)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.908
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND1A	NM_001352964.2	c.303-3672G>A		intron_variant	Intron 5 of 23	ENST00000394215.7	NP_001339893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND1A	ENST00000394215.7	c.303-3672G>A		intron_variant	Intron 5 of 23	5	NM_001352964.2	ENSP00000377763.4

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52043 AN: 152056 Hom.: 9180 Cov.: 33

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.333

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.342 AC: 52114 AN: 152174 Hom.: 9197 Cov.: 33 AF XY: 0.348 AC XY: 25914 AN XY: 74404

African (AFR) AF: 0.394 AC: 16336 AN: 41506

American (AMR) AF: 0.357 AC: 5456 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1114 AN: 3472

East Asian (EAS) AF: 0.133 AC: 689 AN: 5178

South Asian (SAS) AF: 0.271 AC: 1310 AN: 4832

European-Finnish (FIN) AF: 0.429 AC: 4539 AN: 10590

Middle Eastern (MID) AF: 0.331 AC: 96 AN: 290

European-Non Finnish (NFE) AF: 0.318 AC: 21594 AN: 67992

Other (OTH) AF: 0.330 AC: 697 AN: 2110

Alfa AF: 0.326 Hom.: 2810

Bravo AF: 0.340

Asia WGS AF: 0.230 AC: 801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.8
DANN	Benign	0.78
PhyloP100		0.91
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: rs10986087; hg19: chr9-126442740;