Variant 1-206393546-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BP4_Strong

The NM_015326.5(SRGAP2):c.704G>A(p.Arg235His) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R235R) has been classified as Benign.

Frequency

Genomes: not found (cov: 20)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

SRGAP2
NM_015326.5 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 10.0

Variant links:

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]

SRGAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, Cadd, Dann, Eigen, phyloP100way_vertebrate, PrimateAI [when BayesDel_noAF, MetaRNN was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.009718627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRGAP2	NM_015326.5 linkuse as main transcript	c.704G>A	p.Arg235His	missense_variant, splice_region_variant	7/23	ENST00000573034.8	NP_056141.2	O75044B4DFE5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SRGAP2	ENST00000573034.8 linkuse as main transcript	c.704G>A	p.Arg235His	missense_variant, splice_region_variant	7/23	1	NM_015326.5	ENSP00000459615.2	O75044
SRGAP2	ENST00000624873.3 linkuse as main transcript	c.704G>A	p.Arg235His	missense_variant, splice_region_variant	6/22	1		ENSP00000485517.1	B7ZM87
SRGAP2	ENST00000605610.5 linkuse as main transcript	c.704G>A	p.Arg235His	missense_variant, splice_region_variant	6/20	2		ENSP00000473954.1	A0A075B7B5
SRGAP2	ENST00000419187.6 linkuse as main transcript	c.245G>A	p.Arg82His	missense_variant, splice_region_variant	4/7	5		ENSP00000397990.3	E9PDX4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00294

AC:

617

AN:

209880

Hom.:

AF XY:

0.00271

AC XY:

310

AN XY:

114452

show subpopulations

Gnomad AFR exome

AF:

0.000366

Gnomad AMR exome

AF:

0.00581

Gnomad ASJ exome

AF:

0.00300

Gnomad EAS exome

AF:

0.00681

Gnomad SAS exome

AF:

0.00368

Gnomad FIN exome

AF:

0.000198

Gnomad NFE exome

AF:

0.00235

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00000319

AC:

AN:

626626

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

341334

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000286

Gnomad4 OTH exome

AF:

0.0000303

GnomAD4 genome

Cov.:

Alfa

AF:

0.00986

Hom.:

ExAC

AF:

0.0140

AC:

1689

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Intellectual disability

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Lars Feuk Lab, Uppsala University

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

.;.;T;T

Eigen

Pathogenic

1.2

Eigen_PC

Pathogenic

1.0

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

D;D;D;D

MetaRNN

Benign

0.0097

T;T;T;T

MetaSVM

Uncertain

-0.21

PrimateAI

Pathogenic

0.89

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

.;.;.;D

Vest4

0.34

ClinPred

0.056

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.55

gMVP

0.75

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over