Genetic Variant SRGAP2:c.2360+102G>T (chr1-206453482-G-T) – ACMG Classification: Likely_benign (-4 pts)

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.445

Publications

12 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 -4 ACMG points.

BP4

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

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	Effect	Exon Rank	Protein	UniProt
SRGAP2	NM_015326.5	MANE Select	c.2360+102G>T	intron	N/A	NP_056141.2	O75044
SRGAP2	NM_001170637.4		c.2357+102G>T	intron	N/A	NP_001164108.1	B7ZM87
SRGAP2	NM_001377444.1		c.2360+102G>T	intron	N/A	NP_001364373.1	A0A1S5UZH8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SRGAP2	ENST00000573034.8	TSL:1 MANE Select	c.2360+102G>T	intron	N/A	ENSP00000459615.2	O75044
SRGAP2	ENST00000624873.3	TSL:1	c.2357+102G>T	intron	N/A	ENSP00000485517.1	B7ZM87
SRGAP2	ENST00000605476.5	TSL:1	c.1202+102G>T	intron	N/A	ENSP00000474270.1	Q5VZB4

Frequencies

GnomAD3 genomes

AF:

0.000218

AC:

AN:

151214

Hom.:

Cov.:

show subpopulations

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:

AN:

318304

Hom.:

Cov.:

AF XY:

0.0000121

AC XY:

AN XY:

165806

show subpopulations

African (AFR)

AF:

0.000919

AC:

AN:

7620

American (AMR)

AF:

0.00

AC:

AN:

9160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10192

East Asian (EAS)

AF:

0.00

AC:

AN:

23350

South Asian (SAS)

AF:

0.00

AC:

AN:

19974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1814

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

187222

Other (OTH)

AF:

0.0000529

AC:

AN:

18914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000218

AC:

AN:

151214

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

AN XY:

73750

show subpopulations

African (AFR)

AF:

0.000780

AC:

AN:

41046

American (AMR)

AF:

0.0000658

AC:

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5082

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67918

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

(source)

PhyloP100

0.45

PromoterAI

0.019

Neutral

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over