rs6940729

Variant names:

• chr6-47585184-T-A
• rs6940729
• NM_012120.3:c.1108+3119T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-47585184-T-A
• chr6-47585184-T-C
• chr6-47585184-T-G

Variant summary

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

The NM_012120.3(CD2AP):​c.1108+3119T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 149,864 control chromosomes in the GnomAD database, including 28,227 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 0.61 (28227 hom., cov: 28)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 6 publications found

Genes affected

CD2AP (HGNC:14258): (CD2 associated protein) This gene encodes a scaffolding molecule that regulates the actin cytoskeleton. The protein directly interacts with filamentous actin and a variety of cell membrane proteins through multiple actin binding sites, SH3 domains, and a proline-rich region containing binding sites for SH3 domains. The cytoplasmic protein localizes to membrane ruffles, lipid rafts, and the leading edges of cells. It is implicated in dynamic actin remodeling and membrane trafficking that occurs during receptor endocytosis and cytokinesis. Haploinsufficiency of this gene is implicated in susceptibility to glomerular disease. [provided by RefSeq, Jul 2008]

CD2AP Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis 3, susceptibility to

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• inherited focal segmental glomerulosclerosis

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012120.3. 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
	CD2AP	NM_012120.3	MANE Select	c.1108+3119T>A		intron	N/A	NP_036252.1	Q9Y5K6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	ENST00000359314.5	TSL:1 MANE Select	c.1108+3119T>A		intron	N/A	ENSP00000352264.5	Q9Y5K6
	CD2AP	ENST00000865253.1		c.1111+3119T>A		intron	N/A	ENSP00000535312.1
	CD2AP	ENST00000931707.1		c.1099+3119T>A		intron	N/A	ENSP00000601766.1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 90706 AN: 149770 Hom.: 28217 Cov.: 28

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.606 AC: 90751 AN: 149864 Hom.: 28227 Cov.: 28 AF XY: 0.597 AC XY: 43620 AN XY: 73080

African (AFR) AF: 0.530 AC: 21707 AN: 40972

American (AMR) AF: 0.517 AC: 7823 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2409 AN: 3444

East Asian (EAS) AF: 0.299 AC: 1510 AN: 5058

South Asian (SAS) AF: 0.648 AC: 3089 AN: 4764

European-Finnish (FIN) AF: 0.594 AC: 5957 AN: 10032

Middle Eastern (MID) AF: 0.748 AC: 214 AN: 286

European-Non Finnish (NFE) AF: 0.687 AC: 46197 AN: 67210

Other (OTH) AF: 0.629 AC: 1303 AN: 2072

Alfa AF: 0.624 Hom.: 3506

Bravo AF: 0.593

Asia WGS AF: 0.472 AC: 1635 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.53
PhyloP100		0.21
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: rs6940729; hg19: chr6-47552920;