rs2580520

Positions:

• chr1-121370191-C-G
• chr1-121370191-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001329984.2(SRGAP2C):​c.487-3780C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.16 (449 hom., cov: 7)
  • Failed GnomAD Quality Control
• Consequence: SRGAP2C NM_001329984.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

Genes affected

SRGAP2C (HGNC:30584): (SLIT-ROBO Rho GTPase activating protein 2C) This locus encodes a member of the SLIT-ROBO Rho GTPase activating protein family. This human-specific locus resulted from segmental duplication of the SLIT-ROBO Rho GTPase activating protein 2B locus. The encoded protein lacks the GTPase activating protein domain compared to proteins encoded by SLIT-ROBO Rho GTPase activating protein 2, and acts antagonistically to these proteins in cortical neuron development. [provided by RefSeq, Dec 2012]

SRGAP2-AS1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRGAP2C	NM_001329984.2	c.487-3780C>G		intron_variant		ENST00000367123.8	NP_001316913.1
SRGAP2C	NM_001271872.3	c.487-3780C>G		intron_variant			NP_001258801.1
SRGAP2-AS1	NR_104189.1	n.330-7303G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRGAP2C	ENST00000367123.8	c.487-3780C>G		intron_variant		5	NM_001329984.2	ENSP00000478290.1
SRGAP2C	ENST00000304465.7	c.28-3780C>G		intron_variant		5		ENSP00000483477.1
SRGAP2-AS1	ENST00000437515.1	n.330-7303G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 8032 AN: 51490 Hom.: 452 Cov.: 7 FAILED QC

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0856

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.157

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.156 AC: 8026 AN: 51546 Hom.: 449 Cov.: 7 AF XY: 0.145 AC XY: 3580 AN XY: 24610

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0856

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.151

Alfa AF: 0.557 Hom.: 2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2580520; hg19: chr1-121112052;