Genetic Variant SRGAP2:p.His307Leu (chr1-206401509-A-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_015326.5(SRGAP2):c.920A>T(p.His307Leu) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 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: 𝑓 0.0 ( 0 hom., cov: 22)

Failed GnomAD Quality Control

Consequence

SRGAP2
NM_015326.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.32

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2686534).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRGAP2	NM_015326.5	MANE Select	c.920A>T	p.His307Leu	missense	Exon 8 of 23	NP_056141.2	O75044
SRGAP2	NM_001170637.4		c.917A>T	p.His306Leu	missense	Exon 8 of 23	NP_001164108.1	B7ZM87
SRGAP2	NM_001377444.1		c.920A>T	p.His307Leu	missense	Exon 8 of 24	NP_001364373.1	A0A1S5UZH8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRGAP2	ENST00000573034.8	TSL:1 MANE Select	c.920A>T	p.His307Leu	missense	Exon 8 of 23	ENSP00000459615.2	O75044
SRGAP2	ENST00000624873.3	TSL:1	c.917A>T	p.His306Leu	missense	Exon 7 of 22	ENSP00000485517.1	B7ZM87
SRGAP2	ENST00000934486.1		c.917A>T	p.His306Leu	missense	Exon 8 of 24	ENSP00000604545.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148282

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

148282

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72134

African (AFR)

AF:

0.00

AC:

AN:

40068

American (AMR)

AF:

0.00

AC:

AN:

14818

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3432

East Asian (EAS)

AF:

0.00

AC:

AN:

5076

South Asian (SAS)

AF:

0.00

AC:

AN:

4350

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67064

Other (OTH)

AF:

0.00

AC:

AN:

1956

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.078

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.0

PhyloP100

9.3

PrimateAI

Pathogenic

0.84

Sift4G

Benign

0.19

Polyphen

0.012

Vest4

0.57

MutPred

0.30

Loss of disorder (P = 0.0652)

MVP

0.36

ClinPred

0.99

GERP RS

6.0

Varity_R

0.73

gMVP

0.73

Mutation Taster

=99/1

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over