chr9-123555360-G-A

Position:

• chr9-123555360-G-A

Variant summary

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

The NM_001352964.2(DENND1A):​c.993+2210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 152,184 control chromosomes in the GnomAD database, including 68 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 0.021 (68 hom., cov: 32)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DENND1A	NM_001352964.2	c.993+2210C>T		intron_variant		ENST00000394215.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DENND1A	ENST00000394215.7	c.993+2210C>T		intron_variant		5	NM_001352964.2	A2

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3155 AN: 152066 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0624

Gnomad SAS AF: 0.00499

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.0187

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

GnomAD4 genome AF: 0.0207 AC: 3150 AN: 152184 Hom.: 68 Cov.: 32 AF XY: 0.0210 AC XY: 1565 AN XY: 74406

Gnomad4 AFR AF: 0.0570

Gnomad4 AMR AF: 0.00915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0622

Gnomad4 SAS AF: 0.00499

Gnomad4 FIN AF: 0.0166

Gnomad4 NFE AF: 0.00118

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.00833 Hom.: 18

Bravo AF: 0.0220

Asia WGS AF: 0.0390 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.74

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: rs7037102; hg19: chr9-126317639;