9-123389670-G-T

Variant names:

• chr9-123389670-G-T
• rs10985997
• NM_001352964.2:c.1632-1812C>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.1632-1812C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,292 control chromosomes in the GnomAD database, including 1,229 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 0.12 (1229 hom., cov: 33)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

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 (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND1A	NM_001352964.2	c.1632-1812C>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.1632-1812C>A		intron_variant	Intron 21 of 23	5	NM_001352964.2	ENSP00000377763.4
DENND1A	ENST00000473039.5	n.1441-1812C>A		intron_variant	Intron 15 of 17	1
DENND1A	ENST00000373624.6	c.1578-5757C>A		intron_variant	Intron 20 of 21	5		ENSP00000362727.2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17565 AN: 152174 Hom.: 1224 Cov.: 33

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0847

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.115 AC: 17582 AN: 152292 Hom.: 1229 Cov.: 33 AF XY: 0.116 AC XY: 8623 AN XY: 74444

African (AFR) AF: 0.0529 AC: 2198 AN: 41576

American (AMR) AF: 0.0846 AC: 1295 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3470

East Asian (EAS) AF: 0.275 AC: 1428 AN: 5188

South Asian (SAS) AF: 0.160 AC: 771 AN: 4828

European-Finnish (FIN) AF: 0.129 AC: 1366 AN: 10594

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9578 AN: 68002

Other (OTH) AF: 0.128 AC: 270 AN: 2116

Alfa AF: 0.131 Hom.: 4573

Bravo AF: 0.111

Asia WGS AF: 0.229 AC: 794 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	0.026
DANN	Benign	0.34
PhyloP100		-2.4
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

Publications

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Other links and lift over

dbSNP: rs10985997; hg19: chr9-126151949;