rs7852296

Positions:

• chr9-123589939-G-A
• chr9-123589939-G-C
• chr9-123589939-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352964.2(DENND1A):​c.766-6669C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,248 control chromosomes in the GnomAD database, including 999 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 0.11 (999 hom., cov: 32)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND1A	NM_001352964.2	c.766-6669C>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.766-6669C>T		intron_variant		5	NM_001352964.2	ENSP00000377763	A2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16428 AN: 152130 Hom.: 989 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.0893

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0713

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0928

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.108 AC: 16472 AN: 152248 Hom.: 999 Cov.: 32 AF XY: 0.108 AC XY: 8027 AN XY: 74428

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0890

Gnomad4 ASJ AF: 0.0922

Gnomad4 EAS AF: 0.0890

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.0713

Gnomad4 NFE AF: 0.0928

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0913 Hom.: 705

Bravo AF: 0.111

Asia WGS AF: 0.107 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.26

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: rs7852296; hg19: chr9-126352218;