chr1-206415972-A-T

Position:

• chr1-206415972-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015326.5(SRGAP2):​c.1440A>T​(p.Glu480Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRGAP2 NM_015326.5 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4157046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRGAP2	NM_015326.5	c.1440A>T	p.Glu480Asp	missense_variant, splice_region_variant	11/23	ENST00000573034.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRGAP2	ENST00000573034.8	c.1440A>T	p.Glu480Asp	missense_variant, splice_region_variant	11/23	1	NM_015326.5	P5
SRGAP2	ENST00000624873.3	c.1437A>T	p.Glu479Asp	missense_variant, splice_region_variant	10/22	1		A1
SRGAP2	ENST00000605476.5	c.282A>T	p.Glu94Asp	missense_variant, splice_region_variant	2/12	1
SRGAP2	ENST00000605610.5	c.1437A>T	p.Glu479Asp	missense_variant, splice_region_variant	10/20	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

SRGAP2: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.0026	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	.;T;T;.
Eigen	Pathogenic	0.78
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;D;D;D
MetaRNN	Benign	0.42	T;T;T;T
MetaSVM	Benign	-0.80	T
PrimateAI	Uncertain	0.78	T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.029	.;.;B;.
Vest4		0.63
MutPred		0.22		.;.;Loss of methylation at K476 (P = 0.1444);.;
MVP		0.40
ClinPred		0.96	D
GERP RS		3.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.67
gMVP		0.40

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-206589332;