1-206401508-CAT-TTG

Variant names:

• chr1-206401508-CAT-TTG
• NM_015326.5:c.919_921delCATinsTTG
• SRGAP2 p.His307Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_015326.5(SRGAP2):​c.919_921delCATinsTTG​(p.His307Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H307P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: SRGAP2 NM_015326.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015326.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRGAP2	NM_015326.5	MANE Select	c.919_921delCATinsTTG	p.His307Leu	missense	N/A	NP_056141.2	O75044
	SRGAP2	NM_001170637.4		c.916_918delCATinsTTG	p.His306Leu	missense	N/A	NP_001164108.1	B7ZM87
	SRGAP2	NM_001377444.1		c.919_921delCATinsTTG	p.His307Leu	missense	N/A	NP_001364373.1	A0A1S5UZH8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRGAP2	ENST00000573034.8	TSL:1 MANE Select	c.919_921delCATinsTTG	p.His307Leu	missense	N/A	ENSP00000459615.2	O75044
	SRGAP2	ENST00000624873.3	TSL:1	c.916_918delCATinsTTG	p.His306Leu	missense	N/A	ENSP00000485517.1	B7ZM87
	SRGAP2	ENST00000934486.1		c.916_918delCATinsTTG	p.His306Leu	missense	N/A	ENSP00000604545.1

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-206574867;