rs10858049

Variant names:

• chr1-114653545-A-G
• rs10858049
• NM_001256404.2:c.-317+960T>C

Variant summary

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

The NM_001256404.2(DENND2C):​c.-317+960T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,170 control chromosomes in the GnomAD database, including 4,206 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 0.22 (4206 hom., cov: 32)
• Consequence: DENND2C NM_001256404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460
• Publications: 3 publications found

Genes affected

DENND2C (HGNC:24748): (DENN domain containing 2C) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256404.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2C	NM_001256404.2	MANE Select	c.-317+960T>C		intron	N/A	NP_001243333.1
	DENND2C	NM_198459.4		c.-205+16438T>C		intron	N/A	NP_940861.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2C	ENST00000393274.6	TSL:5 MANE Select	c.-317+960T>C		intron	N/A	ENSP00000376955.1
	DENND2C	ENST00000393276.7	TSL:5	c.-205+16438T>C		intron	N/A	ENSP00000376957.3
	DENND2C	ENST00000493549.1	TSL:3	n.182+16696T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32785 AN: 152054 Hom.: 4208 Cov.: 32

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.215 AC: 32781 AN: 152170 Hom.: 4206 Cov.: 32 AF XY: 0.213 AC XY: 15818 AN XY: 74390

African (AFR) AF: 0.0964 AC: 4003 AN: 41520

American (AMR) AF: 0.213 AC: 3262 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 572 AN: 3470

East Asian (EAS) AF: 0.100 AC: 520 AN: 5184

South Asian (SAS) AF: 0.132 AC: 639 AN: 4830

European-Finnish (FIN) AF: 0.283 AC: 2993 AN: 10580

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20212 AN: 67992

Other (OTH) AF: 0.173 AC: 366 AN: 2110

Alfa AF: 0.266 Hom.: 9004

Bravo AF: 0.204

Asia WGS AF: 0.141 AC: 488 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.46
PhyloP100		0.46
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: rs10858049; hg19: chr1-115196166;