rs2336938

Variant names:

• chr1-206445453-C-A
• rs2336938
• NM_015326.5:c.1875-622C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-206445453-C-A
• chr1-206445453-C-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SRGAP2	NM_015326.5	c.1875-622C>A		intron_variant	Intron 17 of 22	ENST00000573034.8	NP_056141.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRGAP2	ENST00000573034.8	c.1875-622C>A		intron_variant	Intron 17 of 22	1	NM_015326.5	ENSP00000459615.2

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

African (AFR) AF: 0.719 AC: 29863 AN: 41514

American (AMR) AF: 0.557 AC: 8516 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1746 AN: 3472

East Asian (EAS) AF: 0.734 AC: 3803 AN: 5180

South Asian (SAS) AF: 0.573 AC: 2764 AN: 4824

European-Finnish (FIN) AF: 0.549 AC: 5792 AN: 10556

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32400 AN: 67990

Other (OTH) AF: 0.539 AC: 1138 AN: 2110

Alfa AF: 0.504 Hom.: 83049

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
PhyloP100		-0.75

Splicing

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

Other links and lift over

dbSNP: rs2336938; hg19: chr1-206618799;