rs2336938

chr1-206445453-C-Achr1-206445453-C-G

Variant summary

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

The NM_015326.5(SRGAP2):c.1875-622C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,142 control chromosomes in the GnomAD database, including 25,609 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 0.57 (25609 hom., cov: 33)
• Consequence: SRGAP2 NM_015326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRGAP2	NM_015326.5	c.1875-622C>A		intron_variant		ENST00000573034.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRGAP2	ENST00000573034.8	c.1875-622C>A		intron_variant		1	NM_015326.5	P5

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86517 AN: 152024 Hom.: 25553 Cov.: 33

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.569 AC: 86629 AN: 152142 Hom.: 25609 Cov.: 33 AF XY: 0.574 AC XY: 42675 AN XY: 74368

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.539

Alfa AF: 0.488 Hom.: 36448

Bravo AF: 0.578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2336938; hg19: chr1-206618799;