rs872863

Variant names:

• chr9-123392075-C-T
• rs872863
• NM_001352964.2:c.1632-4217G>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.1632-4217G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 152,164 control chromosomes in the GnomAD database, including 715 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 0.094 (715 hom., cov: 32)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 16 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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND1A	NM_001352964.2	c.1632-4217G>A		intron_variant	Intron 21 of 23	ENST00000394215.7	NP_001339893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND1A	ENST00000394215.7	c.1632-4217G>A		intron_variant	Intron 21 of 23	5	NM_001352964.2	ENSP00000377763.4
DENND1A	ENST00000473039.5	n.1441-4217G>A		intron_variant	Intron 15 of 17	1
DENND1A	ENST00000373624.6	c.1578-8162G>A		intron_variant	Intron 20 of 21	5		ENSP00000362727.2

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14241 AN: 152046 Hom.: 713 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0376

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0754

Gnomad OTH AF: 0.0996

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

GnomAD4 genome AF: 0.0937 AC: 14256 AN: 152164 Hom.: 715 Cov.: 32 AF XY: 0.0940 AC XY: 6990 AN XY: 74382

African (AFR) AF: 0.121 AC: 5007 AN: 41496

American (AMR) AF: 0.113 AC: 1734 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3470

East Asian (EAS) AF: 0.0375 AC: 194 AN: 5172

South Asian (SAS) AF: 0.105 AC: 505 AN: 4820

European-Finnish (FIN) AF: 0.0770 AC: 815 AN: 10588

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0754 AC: 5130 AN: 68008

Other (OTH) AF: 0.0986 AC: 208 AN: 2110

Alfa AF: 0.0834 Hom.: 1075

Bravo AF: 0.0986

Asia WGS AF: 0.0670 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		0.29
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: rs872863; hg19: chr9-126154354;