9-123523367-C-T

Variant names:

• chr9-123523367-C-T
• rs2564362
• NM_001352964.2:c.993+34203G>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.993+34203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 152,212 control chromosomes in the GnomAD database, including 486 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 0.072 (486 hom., cov: 32)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND1A	NM_001352964.2	c.993+34203G>A		intron_variant	Intron 13 of 23	ENST00000394215.7	NP_001339893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND1A	ENST00000394215.7	c.993+34203G>A		intron_variant	Intron 13 of 23	5	NM_001352964.2	ENSP00000377763.4

Frequencies

GnomAD3 genomes AF: 0.0723 AC: 11002 AN: 152094 Hom.: 487 Cov.: 32

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0734

Gnomad ASJ AF: 0.0615

Gnomad EAS AF: 0.0243

Gnomad SAS AF: 0.0634

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0781

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

GnomAD4 genome AF: 0.0723 AC: 11003 AN: 152212 Hom.: 486 Cov.: 32 AF XY: 0.0705 AC XY: 5248 AN XY: 74422

African (AFR) AF: 0.0283 AC: 1175 AN: 41556

American (AMR) AF: 0.0733 AC: 1120 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0615 AC: 213 AN: 3464

East Asian (EAS) AF: 0.0243 AC: 126 AN: 5182

South Asian (SAS) AF: 0.0635 AC: 306 AN: 4820

European-Finnish (FIN) AF: 0.0858 AC: 909 AN: 10596

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.101 AC: 6885 AN: 68006

Other (OTH) AF: 0.0792 AC: 167 AN: 2108

Alfa AF: 0.0783 Hom.: 441

Bravo AF: 0.0693

Asia WGS AF: 0.0480 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.71
PhyloP100		0.12
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: rs2564362; hg19: chr9-126285646;