rs150577405

Variant names:

• chr1-111195930-C-A
• rs150577405
• NM_024901.5:c.631G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-111195930-C-A
• chr1-111195930-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024901.5(DENND2D):​c.631G>T​(p.Asp211Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D211N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DENND2D NM_024901.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

DENND2D (HGNC:26192): (DENN domain containing 2D) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024901.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2D	NM_024901.5	MANE Select	c.631G>T	p.Asp211Tyr	missense	Exon 6 of 12	NP_079177.2
	DENND2D	NM_001271833.2		c.622G>T	p.Asp208Tyr	missense	Exon 6 of 12	NP_001258762.1	Q9H6A0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2D	ENST00000357640.9	TSL:1 MANE Select	c.631G>T	p.Asp211Tyr	missense	Exon 6 of 12	ENSP00000350266.4	Q9H6A0-1
	DENND2D	ENST00000369752.5	TSL:2	c.622G>T	p.Asp208Tyr	missense	Exon 6 of 12	ENSP00000358767.5	Q9H6A0-2
	DENND2D	ENST00000900292.1		c.553G>T	p.Asp185Tyr	missense	Exon 5 of 11	ENSP00000570351.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251398 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461812 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	0.0088	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.27
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.62		Gain of loop (P = 0.0312)
MVP		0.49
MPC		1.2
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.39
gMVP		0.58
Mutation Taster		=62/38	polymorphism

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: rs150577405; hg19: chr1-111738552;