dbSNP rs587751643: SRGAP2C:p.Thr210Met (chr1-121374113-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001329984.2(SRGAP2C):c.629C>T(p.Thr210Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 7 hom., cov: 12)

Exomes 𝑓: 0.00041 ( 50 hom. )

Failed GnomAD Quality Control

Consequence

SRGAP2C
NM_001329984.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.74

Publications

0 publications found

Variant links:

Genes affected

SRGAP2C (HGNC:30584): (SLIT-ROBO Rho GTPase activating protein 2C) This locus encodes a member of the SLIT-ROBO Rho GTPase activating protein family. This human-specific locus resulted from segmental duplication of the SLIT-ROBO Rho GTPase activating protein 2B locus. The encoded protein lacks the GTPase activating protein domain compared to proteins encoded by SLIT-ROBO Rho GTPase activating protein 2, and acts antagonistically to these proteins in cortical neuron development. [provided by RefSeq, Dec 2012]

SRGAP2C links:

SRGAP2-AS1 (HGNC:40902): (SRGAP2 antisense RNA 1)

SRGAP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052003562).

BP6

Variant 1-121374113-C-T is Benign according to our data. Variant chr1-121374113-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2639057.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 50 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329984.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRGAP2C	NM_001329984.2	MANE Select	c.629C>T	p.Thr210Met	missense	Exon 6 of 10	NP_001316913.1	P0DJJ0
SRGAP2C	NM_001271872.3		c.629C>T	p.Thr210Met	missense	Exon 6 of 10	NP_001258801.1
SRGAP2-AS1	NR_104189.1		n.330-11225G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRGAP2C	ENST00000367123.8	TSL:5 MANE Select	c.629C>T	p.Thr210Met	missense	Exon 6 of 10	ENSP00000478290.1	P0DJJ0
SRGAP2C	ENST00000918137.1		c.629C>T	p.Thr210Met	missense	Exon 5 of 9	ENSP00000588196.1
SRGAP2C	ENST00000304465.7	TSL:5	c.170C>T	p.Thr57Met	missense	Exon 3 of 7	ENSP00000483477.1	A0A087X0L1

Frequencies

GnomAD3 genomes

AF:

0.000385

AC:

AN:

83014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000388

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000477

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00912

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000119

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000369

AC:

AN:

165338

AF XY:

0.000327

show subpopulations

Gnomad AFR exome

AF:

0.000245

Gnomad AMR exome

AF:

0.000314

Gnomad ASJ exome

AF:

0.000116

Gnomad EAS exome

AF:

0.00213

Gnomad FIN exome

AF:

0.0000602

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000406

AC:

168

AN:

413634

Hom.:

Cov.:

AF XY:

0.000425

AC XY:

AN XY:

225962

show subpopulations

African (AFR)

AF:

0.000195

AC:

AN:

10278

American (AMR)

AF:

0.000622

AC:

AN:

24114

Ashkenazi Jewish (ASJ)

AF:

0.0000660

AC:

AN:

15162

East Asian (EAS)

AF:

0.00228

AC:

AN:

16654

South Asian (SAS)

AF:

0.000108

AC:

AN:

55336

European-Finnish (FIN)

AF:

0.0000661

AC:

AN:

30264

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2944

European-Non Finnish (NFE)

AF:

0.000271

AC:

AN:

236572

Other (OTH)

AF:

0.00179

AC:

AN:

22310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000385

AC:

AN:

83092

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

AN XY:

40098

show subpopulations

African (AFR)

AF:

0.000387

AC:

AN:

18094

American (AMR)

AF:

0.000477

AC:

AN:

8382

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2426

East Asian (EAS)

AF:

0.00913

AC:

AN:

1752

South Asian (SAS)

AF:

0.00

AC:

AN:

3180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

200

European-Non Finnish (NFE)

AF:

0.000119

AC:

AN:

42064

Other (OTH)

AF:

0.00

AC:

AN:

1146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.681

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000384

Hom.:

ExAC

AF:

0.000404

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0062

FATHMM_MKL

Benign

0.042

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0052

PhyloP100

2.7

Sift4G

Benign

0.14

Vest4

0.23

MVP

0.14

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.094

gMVP

0.24

Mutation Taster

=100/0

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over