Genetic Variant SRGAP2C:p.Val404Val (chr1-121387687-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_001329984.2(SRGAP2C):c.1212C>T(p.Val404Val) variant causes a synonymous 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 0.000076 ( 0 hom., cov: 15)

Exomes 𝑓: 0.000037 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SRGAP2C
NM_001329984.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -8.68

Variant links:

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]

SRGAP2C links:

SRGAP2-AS1 (HGNC:40902): (SRGAP2 antisense RNA 1)

SRGAP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP7

Synonymous conserved (PhyloP=-8.68 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRGAP2C	NM_001329984.2 link	c.1212C>T	p.Val404Val	synonymous_variant	Exon 10 of 10	ENST00000367123.8	NP_001316913.1	P0DJJ0
SRGAP2C	NM_001271872.3 link	c.1209C>T	p.Val403Val	synonymous_variant	Exon 10 of 10		NP_001258801.1
SRGAP2-AS1	NR_104189.1 link	n.329+9794G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SRGAP2C	ENST00000367123.8 link	c.1212C>T	p.Val404Val	synonymous_variant	Exon 10 of 10	5	NM_001329984.2	ENSP00000478290.1	P0DJJ0
SRGAP2C	ENST00000304465.7 link	c.750C>T	p.Val250Val	synonymous_variant	Exon 7 of 7	5		ENSP00000483477.1	A0A087X0L1
SRGAP2-AS1	ENST00000437515.1 link	n.329+9794G>A		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

131690

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000237

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0132

Gnomad NFE

AF:

0.0000484

Gnomad OTH

AF:

0.000627

GnomAD3 exomes

AF:

0.000160

AC:

AN:

143316

Hom.:

AF XY:

0.000210

AC XY:

AN XY:

76034

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000283

Gnomad EAS exome

AF:

0.0000894

Gnomad SAS exome

AF:

0.000732

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000915

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000368

AC:

AN:

543858

Hom.:

Cov.:

AF XY:

0.0000412

AC XY:

AN XY:

291564

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000312

Gnomad4 SAS exome

AF:

0.0000335

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000229

Gnomad4 OTH exome

AF:

0.0000336

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000759

AC:

AN:

131800

Hom.:

Cov.:

AF XY:

0.0000952

AC XY:

AN XY:

63058

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000237

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000484

Gnomad4 OTH

AF:

0.000618

Alfa

AF:

0.000288

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SRGAP2C: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.6

DANN

Benign

0.88

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over