chr1-206453482-G-T

Variant names:

• chr1-206453482-G-T
• rs2483058
• NM_015326.5:c.2360+102G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015326.5(SRGAP2):​c.2360+102G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000873 in 469,518 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00022 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: SRGAP2 NM_015326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445
• Publications: 12 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRGAP2	NM_015326.5	c.2360+102G>T		intron_variant	Intron 20 of 22	ENST00000573034.8	NP_056141.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRGAP2	ENST00000573034.8	c.2360+102G>T		intron_variant	Intron 20 of 22	1	NM_015326.5	ENSP00000459615.2

Frequencies

GnomAD3 genomes AF: 0.000218 AC: 33 AN: 151214 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000780

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000251 AC: 8 AN: 318304 Hom.: 0 Cov.: 0 AF XY: 0.0000121 AC XY: 2 AN XY: 165806

African (AFR) AF: 0.000919 AC: 7 AN: 7620

American (AMR) AF: 0.00 AC: 0 AN: 9160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10192

East Asian (EAS) AF: 0.00 AC: 0 AN: 23350

South Asian (SAS) AF: 0.00 AC: 0 AN: 19974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1814

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 187222

Other (OTH) AF: 0.0000529 AC: 1 AN: 18914

GnomAD4 genome AF: 0.000218 AC: 33 AN: 151214 Hom.: 0 Cov.: 29 AF XY: 0.000203 AC XY: 15 AN XY: 73750

African (AFR) AF: 0.000780 AC: 32 AN: 41046

American (AMR) AF: 0.0000658 AC: 1 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5082

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67918

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
PhyloP100		0.45
PromoterAI		0.019	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2483058; hg19: chr1-206626828;