rs10818854

Variant names:

• chr9-123684499-G-A
• rs10818854
• NM_001352964.2:c.303-7710C>T

Variant summary

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

The NM_001352964.2(DENND1A):​c.303-7710C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 152,152 control chromosomes in the GnomAD database, including 296 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 0.058 (296 hom., cov: 32)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 53 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND1A	NM_001352964.2	c.303-7710C>T		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.303-7710C>T		intron_variant	Intron 5 of 23	5	NM_001352964.2	ENSP00000377763.4

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8779 AN: 152034 Hom.: 296 Cov.: 32

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.0563

Gnomad SAS AF: 0.0882

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0421

Gnomad OTH AF: 0.0614

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

GnomAD4 genome AF: 0.0577 AC: 8782 AN: 152152 Hom.: 296 Cov.: 32 AF XY: 0.0601 AC XY: 4470 AN XY: 74372

African (AFR) AF: 0.0793 AC: 3291 AN: 41496

American (AMR) AF: 0.0558 AC: 853 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 241 AN: 3466

East Asian (EAS) AF: 0.0560 AC: 290 AN: 5176

South Asian (SAS) AF: 0.0887 AC: 428 AN: 4824

European-Finnish (FIN) AF: 0.0587 AC: 622 AN: 10594

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0421 AC: 2861 AN: 68008

Other (OTH) AF: 0.0608 AC: 128 AN: 2106

Alfa AF: 0.0489 Hom.: 627

Bravo AF: 0.0588

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.33
PhyloP100		0.39
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: rs10818854; hg19: chr9-126446778;