1-121370191-C-G

Variant names:

• chr1-121370191-C-G
• rs2580520
• NM_001329984.2:c.487-3780C>G

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 6 publications found

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:40902): (SRGAP2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329984.2. 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
	SRGAP2C	NM_001329984.2	MANE Select	c.487-3780C>G		intron	N/A	NP_001316913.1
	SRGAP2C	NM_001271872.3		c.487-3780C>G		intron	N/A	NP_001258801.1
	SRGAP2-AS1	NR_104189.1		n.330-7303G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRGAP2C	ENST00000367123.8	TSL:5 MANE Select	c.487-3780C>G		intron	N/A	ENSP00000478290.1
	SRGAP2C	ENST00000304465.7	TSL:5	c.28-3780C>G		intron	N/A	ENSP00000483477.1
	SRGAP2-AS1	ENST00000437515.1	TSL:2	n.330-7303G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.156 AC: 8032 AN: 51490 Hom.: 452 Cov.: 7

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.161 AC: 2352 AN: 14646

American (AMR) AF: 0.164 AC: 794 AN: 4850

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 192 AN: 1336

East Asian (EAS) AF: 0.262 AC: 254 AN: 968

South Asian (SAS) AF: 0.115 AC: 242 AN: 2110

European-Finnish (FIN) AF: 0.0856 AC: 235 AN: 2746

Middle Eastern (MID) AF: 0.227 AC: 25 AN: 110

European-Non Finnish (NFE) AF: 0.159 AC: 3756 AN: 23658

Other (OTH) AF: 0.151 AC: 106 AN: 700

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.557 Hom.: 2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.54
PhyloP100		-0.062

Splicing

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

Other links and lift over

dbSNP: rs2580520; hg19: chr1-121112052;