rs2483058

Positions:

• chr1-206453482-G-C
• chr1-206453482-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015326.5(SRGAP2):​c.2360+102G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 468,832 control chromosomes in the GnomAD database, including 55,507 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 0.51 (20582 hom., cov: 29)
  • Exomes 𝑓: 0.45 (34925 hom.)
• Consequence: SRGAP2 NM_015326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445

Genes affected

SRGAP2 (HGNC:19751): (SLIT-ROBO Rho GTPase activating protein 2) This locus encodes a member of the SLIT-ROBO Rho GTPase activating protein family. The encoded protein stimulates GTPase activity of Rac1, and plays a role in cortical neuron development. This locus has several paralogs on human chromosome 1 resulting from segmental duplication. While this locus itself is conserved among various species, the paralogs are found only in the genus Homo, and not in the genomes of non-human great apes. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRGAP2	NM_015326.5	c.2360+102G>C		intron_variant		ENST00000573034.8	NP_056141.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRGAP2	ENST00000573034.8	c.2360+102G>C		intron_variant		1	NM_015326.5	ENSP00000459615	P5

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76559 AN: 151106 Hom.: 20543 Cov.: 29

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.468

GnomAD4 exome AF: 0.452 AC: 143603 AN: 317608 Hom.: 34925 Cov.: 0 AF XY: 0.450 AC XY: 74423 AN XY: 165448

Gnomad4 AFR exome AF: 0.659

Gnomad4 AMR exome AF: 0.503

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.773

Gnomad4 SAS exome AF: 0.518

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.455

GnomAD4 genome AF: 0.507 AC: 76660 AN: 151224 Hom.: 20582 Cov.: 29 AF XY: 0.514 AC XY: 37954 AN XY: 73800

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.474

Alfa AF: 0.279 Hom.: 601

Bravo AF: 0.516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2483058; hg19: chr1-206626828;